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Clinical Trial Results:
A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination with Methotrexate Therapy, in Subjects with Active Moderate-Severe Rheumatoid Arthritis Despite Treatment with Methotrexate

Summary
EudraCT number	2014-003453-34
Trial protocol	EE DE HU CZ ES GB PL IT
Global end of trial date	29 Dec 2017

Results information
Results version number	v2(current)
This version publication date	18 Apr 2019
First version publication date	02 Jan 2019
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

201755

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Mar 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Dec 2017

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of GSK3196165

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jul 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 42

Country: Number of subjects enrolled

Ukraine: 53

Country: Number of subjects enrolled

Russian Federation: 34

Country: Number of subjects enrolled

Czech Republic: 30

Country: Number of subjects enrolled

Mexico: 17

Country: Number of subjects enrolled

Bulgaria: 14

Country: Number of subjects enrolled

South Africa: 11

Country: Number of subjects enrolled

Estonia: 9

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

Hungary: 4

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

Germany: 1

Worldwide total number of subjects

222

EEA total number of subjects

102

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

198

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study was conducted at a total of 60 sites in 12 countries: Ukraine (11), Poland (10), Russian Federation (10), Mexico (6), Czech Republic (5), Bulgaria (4), South Africa (3), Hungary (3), Estonia (2), Canada (2), United Kingdom (2), and Germany (2) from 23-July-2015 until 29-December-2017.

Screening details

A total of 526 participants were screened of which 304 were screen failures and 222 participants were enrolled in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo liquid (sterile 0.9% weight/volume) sodium chloride solution) 0.6 milliliter (mL) drawn into a small (1 mL syringe) administered subcutaneously in the thigh/abdomen up to 52 weeks in combination with methotrexate (MTX) tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 milligram (mg)/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/ divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

A 0.9% weight by volume (w/v) sodium chloride solution will be used as placebo. Placebo will be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK3196165 will be available as liquid dosage form to be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Methotrexate will be available in tablet or liquid dosage forms to be given orally or administered as subcutaneous injection.

Investigational medicinal product name

Folic (or folinic) acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Folic acid will be available as capsule, tablet or liquid form to be taken orally.

GSK3196165 22.5 mg

Arm description

Participants received GSK3196165 22.5 mg (0.15 mL) liquid drawn into a small (03 mL/0.5 mL syringe) administered subcutaneously in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK3196165 will be available as liquid dosage form to be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Methotrexate will be available in tablet or liquid dosage forms to be given orally or administered as subcutaneous injection.

Investigational medicinal product name

Folic (or folinic) acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Folic acid will be available as capsule, tablet or liquid form to be taken orally.

GSK3196165 45 mg

Arm description

Participants received GSK3196165 45 mg (0.3 mL) liquid drawn into a small (03 mL/0.5 mL syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/ divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK3196165 will be available as liquid dosage form to be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Methotrexate will be available in tablet or liquid dosage forms to be given orally or administered as subcutaneous injection.

Investigational medicinal product name

Folic (or folinic) acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Folic acid will be available as capsule, tablet or liquid form to be taken orally.

GSK3196165 90 mg

Arm description

Participants received GSK3196165 90 mg (0.6 mL) liquid drawn into a small (1 mL syringe) administered subcutaneously in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/ divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK3196165 will be available as liquid dosage form to be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Methotrexate will be available in tablet or liquid dosage forms to be given orally or administered as subcutaneous injection.

Investigational medicinal product name

Folic (or folinic) acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Folic acid will be available as capsule, tablet or liquid form to be taken orally.

GSK3196165 135 mg

Arm description

Participants received GSK3196165 135 mg (0.9 mL) liquid drawn into a small (1 mL syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/ divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK3196165 will be available as liquid dosage form to be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Methotrexate will be available in tablet or liquid dosage forms to be given orally or administered as subcutaneous injection.

Investigational medicinal product name

Folic (or folinic) acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Folic acid will be available as capsule, tablet or liquid form to be taken orally.

GSK3196165 180 mg

Arm description

Participants received GSK3196165 180 mg (1.2 mL) liquid drawn into a small (2 mL/3 mL syringe) administered subcutaneously in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK3196165 will be available as liquid dosage form to be administered subcutaneously into thigh or abdomen.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Methotrexate will be available in tablet or liquid dosage forms to be given orally or administered as subcutaneous injection.

Investigational medicinal product name

Folic (or folinic) acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Folic acid will be available as capsule, tablet or liquid form to be taken orally.

Number of subjects in period 1	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Started	37	37	37	37	37	37
Completed	25	23	27	27	25	23
Not completed	12	14	10	10	12	14
Consent withdrawn by subject	1	5	4	4	5	3
Adverse event, non-fatal	1	1	-	1	-	2
Protocol defined stopping criteria	7	4	3	5	3	3
Lost to follow-up	-	-	2	-	-	1
Lack of efficacy	1	3	1	-	4	4
Protocol deviation	2	1	-	-	-	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

GSK3196165 22.5 mg

Reporting group description

Reporting group title

GSK3196165 45 mg

Reporting group description

Reporting group title

GSK3196165 90 mg

Reporting group description

Reporting group title

GSK3196165 135 mg

Reporting group description

Reporting group title

GSK3196165 180 mg

Reporting group description

Reporting group values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg	Total
Number of subjects	37	37	37	37	37	37	222
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	32	34	31	31	36	34	198
From 65-84 years	5	3	6	6	1	3	24
85 years and over	0	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	50.0 ± 11.33	48.4 ± 11.31	52.8 ± 12.22	52.7 ± 11.28	47.1 ± 10.04	52.3 ± 10.76	-
Sex: Female, Male
Units: Subjects
Female	28	30	33	27	33	29	180
Male	9	7	4	10	4	8	42
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaskan Native\|	2	3	1	2	2	1	11
Black or African American\|	0	3	0	0	0	0	3
White\|	34	30	35	35	34	35	203
American Indian/ Alaskan Native+White\|	1	0	1	0	0	0	2
Black or African American+White\|	0	1	0	0	1	1	3

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

GSK3196165 22.5 mg

Reporting group description

Reporting group title

GSK3196165 45 mg

Reporting group description

Reporting group title

GSK3196165 90 mg

Reporting group description

Reporting group title

GSK3196165 135 mg

Reporting group description

Reporting group title

GSK3196165 180 mg

Reporting group description

Primary: Percentage of participants who achieved disease activity score for 28 different joints with C-reactive protein value (DAS28{CRP}) remission (DAS28 <2.6) at Week 24

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End point title

Percentage of participants who achieved disease activity score for 28 different joints with C-reactive protein value (DAS28{CRP}) remission (DAS28 <2.6) at Week 24

End point description

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant’s response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC – Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 millimeter [mm] visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in [milligrams/liter] mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). ITT population comprised of all participants who were randomized to treatment and who received at least one dose of study treatment (GSK3196165 or placebo).

End point type

Primary

End point timeframe

Week 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[1]	37 ^[2]	37 ^[3]	37 ^[4]	37 ^[5]	37 ^[6]
Units: Percentage of participants
number (not applicable)	3	5	16	19	14	14

Notes
[1] - ITT Population
[2] - ITT Population
[3] - ITT Population
[4] - ITT Population
[5] - ITT Population
[6] - ITT Population

Stat 1

Statistical analysis description

95% Confidence Intervals (CI) were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.547

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

24.52

Stat 2

Statistical analysis description

95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.077

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

62.44

Stat 3

Statistical analysis description

95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.053

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.39

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

72.14

Stat 4

Statistical analysis description

95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.122

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

51.4

Stat 5

Statistical analysis description

95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.134

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

48.83

Secondary: Change from Baseline in DAS28(CRP) at Week 12

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End point title

Change from Baseline in DAS28(CRP) at Week 12

End point description

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant’s response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC – Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity [PtGA]) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants with data available at the indicated time point were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	34 ^[7]	35 ^[8]	33 ^[9]	37 ^[10]	34 ^[11]	36 ^[12]
Units: Scores on a scale
least squares mean (standard error)
CRP\|	-5.21 ± 2.730	-4.75 ± 2.701	-8.57 ± 2.749	-7.79 ± 2.624	-7.71 ± 2.722	-7.21 ± 2.659
PtGA\|	-6.72 ± 3.660	-14.40 ± 3.653	-20.40 ± 3.611	-24.11 ± 3.544	-19.35 ± 3.614	-23.90 ± 3.606
SJC28\|	-2.35 ± 1.093	-4.77 ± 1.085	-5.52 ± 1.080	-6.91 ± 1.056	-5.33 ± 1.080	-8.39 ± 1.070
TJC28\|	-2.81 ± 1.191	-5.11 ± 1.181	-6.73 ± 1.173	-8.53 ± 1.151	-6.43 ± 1.175	-9.13 ± 1.167

Notes
[7] - ITT Population
[8] - ITT Population
[9] - ITT Population
[10] - ITT Population
[11] - ITT Population
[12] - ITT Population

Stat 1

Statistical analysis description

CRP, Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.905 ^[13]

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-7.13

upper limit

8.05

Notes
[13] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

CRP, Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.387 ^[14]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.36

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

4.28

Notes
[14] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

CRP, Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.495 ^[15]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.58

Confidence interval

level

95%

sides

2-sided

lower limit

-10.04

upper limit

4.87

Notes
[15] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

PtGA, Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.14 ^[16]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.68

Confidence interval

level

95%

sides

2-sided

lower limit

-17.92

upper limit

2.55

Notes
[16] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

PtGA, Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.009 ^[17]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.68

Confidence interval

level

95%

sides

2-sided

lower limit

-23.85

upper limit

-3.52

Notes
[17] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

PtGA, Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[18]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-17.4

Confidence interval

level

95%

sides

2-sided

lower limit

-27.44

upper limit

-7.35

Notes
[18] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

SJC28, Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.118 ^[19]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.42

Confidence interval

level

95%

sides

2-sided

lower limit

-5.45

upper limit

0.62

Notes
[19] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

SJC28, Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.041 ^[20]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.17

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

-0.14

Notes
[20] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

SJC28, Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003 ^[21]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.56

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

0.05

Notes
[21] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

TJC28, Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.172 ^[22]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.61

upper limit

1.01

Notes
[22] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

TJC28, Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.02 ^[23]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.92

Confidence interval

level

95%

sides

2-sided

lower limit

-7.22

upper limit

-0.62

Notes
[23] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

TJC28, Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[24]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.72

Confidence interval

level

95%

sides

2-sided

lower limit

-8.98

upper limit

-2.45

Notes
[24] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

CRP, Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.518 ^[25]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.51

Confidence interval

level

95%

sides

2-sided

lower limit

-10.13

upper limit

5.12

Notes
[25] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

CRP, Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.599 ^[26]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.5

upper limit

5.49

Notes
[26] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

PtGA, Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.015 ^[27]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.63

Confidence interval

level

95%

sides

2-sided

lower limit

-22.78

upper limit

-2.48

Notes
[27] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

PtGA, Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[28]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-17.18

Confidence interval

level

95%

sides

2-sided

lower limit

-27.27

upper limit

-7.1

Notes
[28] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

SJC28, Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.054 ^[29]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.98

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

0.05

Notes
[29] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

SJC28, Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[30]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.04

Confidence interval

level

95%

sides

2-sided

lower limit

-9.05

upper limit

-3.02

Notes
[30] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

TJC28, Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.031 ^[31]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.63

Confidence interval

level

95%

sides

2-sided

lower limit

-6.92

upper limit

-0.33

Notes
[31] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

TJC28, Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[32]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.32

Confidence interval

level

95%

sides

2-sided

lower limit

-9.61

upper limit

-3.02

Notes
[32] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Percentage of participants who achieved DAS28(CRP) remission (DAS28 <2.6) at all time points

Top of page

End point title

Percentage of participants who achieved DAS28(CRP) remission (DAS28 <2.6) at all time points

End point description

DAS28(CRP) remission is defined as a DAS28 score of <2.6 points. The DAS index combines information relating to the number of swollen and tender joints. The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant’s response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC – Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome).

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[33]	37 ^[34]	37 ^[35]	37 ^[36]	37 ^[37]	37 ^[38]
Units: Percentage of participants
Week 1\|	0	0	0	0	0	0
Week 2\|	0	0	0	0	0	1
Week 4\|	0	0	0	5	3	4
Week 6\|	5	5	0	5	3	8
Week 8\|	3	0	5	14	5	8
Week 12\|	3	8	5	24	3	16
Week 16\|	0	3	14	27	5	19
Week 20\|	3	0	16	19	14	16
Week 24\|	3	5	16	19	14	14
Week 28\|	3	3	16	16	14	22
Week 32\|	3	5	22	14	11	19
Week 36\|	3	5	19	8	16	19
Week 40\|	0	5	14	14	11	24
Week 44\|	3	5	14	16	14	16
Week 48\|	0	5	14	14	14	19
Week 52\|	3	5	14	11	14	14
Week 62 (follow-up)\|	3	0	8	3	11	19

Notes
[33] - ITT Population
[34] - ITT Population
[35] - ITT Population
[36] - ITT Population
[37] - ITT Population
[38] - ITT Population

Stat 1

Statistical analysis description

Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 2

Statistical analysis description

Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

10.3

Stat 3

Statistical analysis description

Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

1.9

Stat 4

Statistical analysis description

Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

10.3

Stat 5

Statistical analysis description

Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 6

Statistical analysis description

Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 7

Statistical analysis description

Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 8

Statistical analysis description

Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 9

Statistical analysis description

Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 10

Statistical analysis description

Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

6.8

upper limit

36.4

Stat 11

Statistical analysis description

Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 12

Statistical analysis description

Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 13

Statistical analysis description

Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.7

upper limit

41.3

Stat 14

Statistical analysis description

Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 15

Statistical analysis description

Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 16

Statistical analysis description

Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 17

Statistical analysis description

Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 18

Statistical analysis description

Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 19

Statistical analysis description

Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 20

Statistical analysis description

Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 21

Statistical analysis description

Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 22

Statistical analysis description

Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 23

Statistical analysis description

Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 24

Statistical analysis description

Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 25

Statistical analysis description

Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 26

Statistical analysis description

Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 27

Statistical analysis description

Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 28

Statistical analysis description

Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 29

Statistical analysis description

Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 30

Statistical analysis description

Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 31

Statistical analysis description

Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 32

Statistical analysis description

Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 33

Statistical analysis description

Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 34

Statistical analysis description

Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 35

Statistical analysis description

Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 36

Statistical analysis description

Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 37

Statistical analysis description

Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 38

Statistical analysis description

Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 39

Statistical analysis description

Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 40

Statistical analysis description

Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 41

Statistical analysis description

Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 42

Statistical analysis description

Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 43

Statistical analysis description

Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 44

Statistical analysis description

Week 2. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 45

Statistical analysis description

Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 46

Statistical analysis description

Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 47

Statistical analysis description

Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

6.3

Stat 48

Statistical analysis description

Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

14.1

Stat 49

Statistical analysis description

Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 50

Statistical analysis description

Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 51

Statistical analysis description

Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 52

Statistical analysis description

Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 53

Statistical analysis description

Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 54

Statistical analysis description

Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 55

Statistical analysis description

Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 56

Statistical analysis description

Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 57

Statistical analysis description

Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 58

Statistical analysis description

Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 59

Statistical analysis description

Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 60

Statistical analysis description

Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 61

Statistical analysis description

Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 62

Statistical analysis description

Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 63

Statistical analysis description

Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 64

Statistical analysis description

Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 65

Statistical analysis description

Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 66

Statistical analysis description

Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

10.5

upper limit

38.1

Stat 67

Statistical analysis description

Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 68

Statistical analysis description

Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 69

Statistical analysis description

Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 70

Statistical analysis description

Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 71

Statistical analysis description

Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 72

Statistical analysis description

Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 73

Statistical analysis description

Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 74

Statistical analysis description

Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Secondary: Change from Baseline in DAS28(CRP) at all assessment time points

Top of page

End point title

Change from Baseline in DAS28(CRP) at all assessment time points

End point description

DAS28 modification of the original DAS is based on a count of 28 swollen and tender joints used to evaluate a participant’s response to treatment. DAS28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated as: DAS28 (CRP)=0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC–Tender joint Count, SJC=Swollen Joint Count, (GH=participant assessment of disease activity and CRP=C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[39]	37 ^[40]	37 ^[41]	37 ^[42]	37 ^[43]	37 ^[44]
Units: Scores on a scale
least squares mean (standard error)
Week 1; n=35, 36, 33, 35, 34, 37\|	-0.14 ± 0.114	-0.47 ± 0.114	-0.44 ± 0.117	-0.52 ± 0.114	-0.55 ± 0.116	-0.63 ± 0.112
Week 2; n=36, 35, 34, 36, 36, 36\|	-0.37 ± 0.138	-0.64 ± 0.141	-0.69 ± 0.142	-0.78 ± 0.138	-0.84 ± 0.139	-0.88 ± 0.139
Week 4; n=32, 33, 34, 36, 36, 36\|	-0.45 ± 0.169	-0.85 ± 0.169	-1.01 ± 0.167	-1.21 ± 0.163	-1.12 ± 0.164	-1.46 ± 0.164
Week 6; n=35, 34, 34, 36, 33, 36\|	-0.65 ± 0.184	-1.07 ± 0.186	-1.12 ± 0.185	-1.26 ± 0.181	-1.12 ± 0.185	-1.51 ± 0.182
Week 8; n=34, 33, 34, 37, 35, 32\|	-0.61 ± 0.195	-1.04 ± 0.197	-1.40 ± 0.196	-1.44 ± 0.190	-1.51 ± 0.194	-1.72 ± 0.196
Week 12; n=34, 35, 33, 37, 34, 36\|	-0.60 ± 0.232	-1.13 ± 0.231	-1.48 ± 0.233	-1.84 ± 0.225	-1.28 ± 0.230	-1.87 ± 0.228
Week 16; n=8, 16, 20, 24, 18, 36\|	-0.87 ± 0.335	-1.16 ± 0.274	-1.86 ± 0.261	-1.88 ± 0.247	-1.64 ± 0.265	-1.98 ± 0.232
Week 20; n=8, 15, 20, 25, 19, 36\|	-1.23 ± 0.359	-1.30 ± 0.284	-1.81 ± 0.260	-1.89 ± 0.241	-2.00 ± 0.263	-2.03 ± 0.221
Week 24; n=8, 14, 20, 24, 19, 33\|	-0.23 ± 0.402	-1.45 ± 0.322	-1.76 ± 0.288	-1.62 ± 0.269	-1.71 ± 0.291	-2.05 ± 0.246

Notes
[39] - ITT Population.
[40] - ITT Population.
[41] - ITT Population.
[42] - ITT Population.
[43] - ITT Population.
[44] - ITT Population.

Stat 1

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.046 ^[45]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

-0.01

Notes
[45] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.071 ^[46]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

0.03

Notes
[46] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022 ^[47]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

-0.05

Notes
[47] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.16 ^[48]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

0.11

Notes
[48] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.103 ^[49]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

0.07

Notes
[49] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.034 ^[50]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

-0.03

Notes
[50] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.096 ^[51]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

0.07

Notes
[51] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.02 ^[52]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

-0.09

Notes
[52] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[53]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

-0.29

Notes
[53] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.11 ^[54]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

0.1

Notes
[54] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.076 ^[55]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.05

Notes
[55] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.02 ^[56]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.1

Notes
[56] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.128 ^[57]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

0.12

Notes
[57] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[58]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

-0.24

Notes
[58] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003 ^[59]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-1.36

upper limit

-0.29

Notes
[59] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.11 ^[60]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.17

upper limit

0.12

Notes
[60] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.008 ^[61]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-1.53

upper limit

-0.23

Notes
[61] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[62]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.24

Confidence interval

level

95%

sides

2-sided

lower limit

-1.88

upper limit

-0.6

Notes
[62] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.5 ^[63]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.15

upper limit

0.56

Notes
[63] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.021 ^[64]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-1.83

upper limit

-0.15

Notes
[64] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 21

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.017 ^[65]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.83

upper limit

-0.18

Notes
[65] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 22

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.871 ^[66]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.83

Notes
[66] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 23

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.19 ^[67]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-1.46

upper limit

0.29

Notes
[67] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 24

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.13 ^[68]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

0.2

Notes
[68] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 25

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.019 ^[69]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

-0.2

Notes
[69] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 26

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002 ^[70]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.51

upper limit

-0.55

Notes
[70] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 27

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[71]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.39

Confidence interval

level

95%

sides

2-sided

lower limit

-2.34

upper limit

-0.43

Notes
[71] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 28

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.013 ^[72]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.09

Notes
[72] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 29

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003 ^[73]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

-0.17

Notes
[73] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 30

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.017 ^[74]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

-0.09

Notes
[74] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 31

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.009 ^[75]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.13

Notes
[75] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 32

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[76]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.2

Notes
[76] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 33

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[77]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.48

upper limit

-0.55

Notes
[77] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 34

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.073 ^[78]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

0.04

Notes
[78] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 35

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[79]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-1.36

upper limit

-0.34

Notes
[79] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 36

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[80]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

-0.35

Notes
[80] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 37

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[81]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.65

upper limit

-0.56

Notes
[81] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 38

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.039 ^[82]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.32

upper limit

-0.03

Notes
[82] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 39

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[83]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.27

Confidence interval

level

95%

sides

2-sided

lower limit

-1.91

upper limit

-0.63

Notes
[83] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 40

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.073 ^[84]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

0.07

Notes
[84] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 41

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007 ^[85]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.11

Confidence interval

level

95%

sides

2-sided

lower limit

-1.91

upper limit

-0.3

Notes
[85] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 42

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.083 ^[86]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.65

upper limit

0.1

Notes
[86] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 43

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.059 ^[87]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

0.03

Notes
[87] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 44

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003 ^[88]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.48

Confidence interval

level

95%

sides

2-sided

lower limit

-2.46

upper limit

-0.5

Notes
[88] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 45

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[89]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.82

Confidence interval

level

95%

sides

2-sided

lower limit

-2.75

upper limit

-0.89

Notes
[89] - MMRM analysis adjusted for DAS28(CRP) Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Time to first DAS28(CRP) remission

Top of page

End point title

Time to first DAS28(CRP) remission

End point description

DAS28 modification of the original DAS is based on a count of 28 swollen and tender joints used to evaluate a participant’s response to treatment. DAS28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated as: DAS28 (CRP)=0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC–Tender joint Count, SJC=Swollen Joint Count, (GH=participant assessment of disease activity and CRP=C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline. Only those participants with data available at the time of assessment were analyzed. Median time, to remission has been presented.

End point type

Secondary

End point timeframe

Up to Week 62

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	4 ^[90]	6 ^[91]	11 ^[92]	10 ^[93]	7 ^[94]	18 ^[95]
Units: Weeks
median (full range (min-max))
Time to DAS (CRP28)	9.10 (6.0 to 20.3)	12.05 (6.1 to 24.3)	16.10 (8.0 to 24.9)	8.10 (4.1 to 16.3)	19.90 (4.3 to 24.9)	18.20 (2.0 to 64.1)

Notes
[90] - ITT Population.
[91] - ITT Population.
[92] - ITT Population.
[93] - ITT Population.
[94] - ITT Population.
[95] - ITT Population.

No statistical analyses for this end point

Secondary: Percentage of participants achieving categorical DAS28(CRP) response (moderate/good [European League against Rheumatism] EULAR response) at all assessment time points

Top of page

End point title

Percentage of participants achieving categorical DAS28(CRP) response (moderate/good [European League against Rheumatism] EULAR response) at all assessment time points

End point description

DAS28(CRP) scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as follows: Current DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2=good response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response). Current DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline value (>1.2 =moderate response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response). Current DAS28 >5.1 and DAS28 decrease from Baseline value (>1.2=moderate response), (>0.6 to <=1.2 = no response) and (<=0.6 =no response). If the post-Baseline DAS28(CRP) score was missing, then the corresponding EULAR category was set to missing.

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[96]	37 ^[97]	37 ^[98]	37 ^[99]	37 ^[100]	37 ^[101]
Units: Percentage of participants
Week 1\|	5	22	16	24	19	27
Week 2\|	14	19	16	38	32	38
Week 4\|	16	46	38	46	43	68
Week 6\|	24	46	43	51	46	65
Week 8\|	32	43	59	65	59	68
Week 12\|	22	43	51	68	49	76
Week 16\|	22	35	54	59	43	73
Week 20\|	16	35	51	65	43	73
Week 24\|	16	32	46	54	43	70
Week 28\|	3	8	19	19	16	78
Week 32\|	3	8	22	22	16	73
Week 36\|	3	8	19	22	16	73
Week 40\|	3	8	19	22	16	65
Week 44\|	3	8	19	19	16	59
Week 48\|	3	8	19	19	16	65
Week 52\|	3	8	16	16	16	51
Week 62 (follow-up)\|	3	5	16	16	16	54

Notes
[96] - ITT Population
[97] - ITT Population
[98] - ITT Population
[99] - ITT Population
[100] - ITT Population
[101] - ITT Population

Stat 1

Statistical analysis description

Difference to placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.037

Method

Regression, Logistic

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

31.4

Stat 2

Statistical analysis description

Difference to placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.144

Method

Regression, Logistic

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

24.7

Stat 3

Statistical analysis description

Difference to placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.033

Method

Regression, Logistic

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

3.3

upper limit

34.5

Stat 4

Statistical analysis description

Difference to placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.437

Method

Regression, Logistic

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-11.3

upper limit

22.2

Stat 5

Statistical analysis description

Difference to placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.755

Method

Regression, Logistic

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-13.5

upper limit

18.9

Stat 6

Statistical analysis description

Difference to placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.023

Method

Regression, Logistic

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

5.2

upper limit

43.4

Stat 7

Statistical analysis description

Difference to placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

49.7

Stat 8

Statistical analysis description

Difference to placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.039

Method

Regression, Logistic

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

41.2

Stat 9

Statistical analysis description

Difference to placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.008

Method

Regression, Logistic

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

49.7

Stat 10

Statistical analysis description

Difference to placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.044

Method

Regression, Logistic

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

42.8

Stat 11

Statistical analysis description

Difference to placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.083

Method

Regression, Logistic

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

Stat 12

Statistical analysis description

Difference to placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.8

upper limit

48.3

Stat 13

Statistical analysis description

Difference to placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-11.2

upper limit

32.8

Stat 14

Statistical analysis description

Difference to placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.2

upper limit

48.9

Stat 15

Statistical analysis description

Difference to placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

32.4

Confidence interval

level

95%

sides

2-sided

lower limit

10.9

upper limit

Stat 16

Statistical analysis description

Difference to placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

42.4

Stat 17

Statistical analysis description

Difference to placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

8.9

upper limit

50.6

Stat 18

Statistical analysis description

Difference to placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

45.9

Confidence interval

level

95%

sides

2-sided

lower limit

25.9

upper limit

Stat 19

Statistical analysis description

Difference to placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

sides

2-sided

lower limit

-6.8

upper limit

33.8

Stat 20

Statistical analysis description

Difference to placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

32.4

Confidence interval

level

95%

sides

2-sided

lower limit

11.6

upper limit

53.3

Stat 21

Statistical analysis description

Difference to placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

17.2

upper limit

58.5

Stat 22

Statistical analysis description

Difference to placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

38.4

Stat 23

Statistical analysis description

Difference to placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

35.1

Confidence interval

level

95%

sides

2-sided

lower limit

15.1

upper limit

55.1

Stat 24

Statistical analysis description

Difference to placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

48.6

Confidence interval

level

95%

sides

2-sided

lower limit

29.2

upper limit

68.1

Stat 25

Statistical analysis description

Difference to placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

35.4

Stat 26

Statistical analysis description

Difference to placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

49.7

Stat 27

Statistical analysis description

Difference to placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

17.9

upper limit

57.8

Stat 28

Statistical analysis description

Difference to placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 29

Statistical analysis description

Difference to placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 30

Statistical analysis description

Difference to placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 31

Statistical analysis description

Difference to placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 32

Statistical analysis description

Difference to placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 33

Statistical analysis description

Difference to placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 34

Statistical analysis description

Difference to placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 35

Statistical analysis description

Difference to placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 36

Statistical analysis description

Difference to placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 37

Statistical analysis description

Difference to placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 38

Statistical analysis description

Difference to placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 39

Statistical analysis description

Difference to placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 40

Statistical analysis description

Difference to placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 41

Statistical analysis description

Difference to placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 42

Statistical analysis description

Difference to placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 43

Statistical analysis description

Difference to placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 44

Statistical analysis description

Difference to placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 45

Statistical analysis description

Difference to placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 46

Statistical analysis description

Difference to placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 47

Statistical analysis description

Difference to placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 48

Statistical analysis description

Difference to placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 49

Statistical analysis description

Difference to placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 50

Statistical analysis description

Difference to placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

5.6

upper limit

37.7

Stat 51

Statistical analysis description

Difference to placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

37.6

Stat 52

Statistical analysis description

Difference to placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

5.2

upper limit

43.4

Stat 53

Statistical analysis description

Difference to placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.1

upper limit

46.9

Stat 54

Statistical analysis description

Difference to placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

32.2

upper limit

70.5

Stat 55

Statistical analysis description

Difference to placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

42.8

Stat 56

Statistical analysis description

Difference to placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

40.5

Confidence interval

level

95%

sides

2-sided

lower limit

19.9

upper limit

61.2

Stat 57

Statistical analysis description

Difference to placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.2

upper limit

48.9

Stat 58

Statistical analysis description

Difference to placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

35.1

Confidence interval

level

95%

sides

2-sided

lower limit

13.8

upper limit

56.5

Stat 59

Statistical analysis description

Difference to placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

6.2

upper limit

47.9

Stat 60

Statistical analysis description

Difference to placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

54.1

Confidence interval

level

95%

sides

2-sided

lower limit

34.9

upper limit

73.2

Stat 61

Statistical analysis description

Difference to placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

42.4

Stat 62

Statistical analysis description

Difference to placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

31.8

upper limit

70.9

Stat 63

Statistical analysis description

Difference to placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.1

upper limit

46.9

Stat 64

Statistical analysis description

Difference to placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

56.8

Confidence interval

level

95%

sides

2-sided

lower limit

38.2

upper limit

75.4

Stat 65

Statistical analysis description

Difference to placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.1

upper limit

46.9

Stat 66

Statistical analysis description

Difference to placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

54.1

Confidence interval

level

95%

sides

2-sided

lower limit

35.1

upper limit

Stat 67

Statistical analysis description

Difference to placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 68

Statistical analysis description

Difference to placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

75.7

Confidence interval

level

95%

sides

2-sided

lower limit

61.4

upper limit

89.9

Stat 69

Statistical analysis description

Difference to placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 70

Statistical analysis description

Difference to placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

70.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

85.5

Stat 71

Statistical analysis description

Difference to placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 72

Statistical analysis description

Difference to placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

70.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

85.5

Stat 73

Statistical analysis description

Difference to placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 74

Statistical analysis description

Difference to placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

62.2

Confidence interval

level

95%

sides

2-sided

lower limit

45.9

upper limit

78.4

Stat 75

Statistical analysis description

Difference to placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 76

Statistical analysis description

Difference to placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

56.8

Confidence interval

level

95%

sides

2-sided

lower limit

40.1

upper limit

73.4

Stat 77

Statistical analysis description

Difference to placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 78

Statistical analysis description

Difference to placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

62.2

Confidence interval

level

95%

sides

2-sided

lower limit

45.9

upper limit

78.4

Stat 79

Statistical analysis description

Difference to placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 80

Statistical analysis description

Difference to placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

48.6

Confidence interval

level

95%

sides

2-sided

lower limit

31.7

upper limit

65.6

Stat 81

Statistical analysis description

Difference to placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 82

Statistical analysis description

Difference to placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

34.5

upper limit

68.2

Secondary: Percentage of participants with American College of Rheumatology’s (ACR) 20/50/70 response rates at all assessment time points

Top of page

End point title

Percentage of participants with American College of Rheumatology’s (ACR) 20/50/70 response rates at all assessment time points

End point description

The ACR definition for calculating improvement in rheumatoid arthritis is calculated as a 20% improvement (ACR20) in both tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR-core set measures: participant and physician global assessments, participant's assessment of arthritis pain, disability, and an acute-phase reactant (i.e. CRP value). Similarly, ACR50 and ACR70 were calculated with the respective percent improvement. The specific components of the ACR assessments are as follows: Tender/Painful Joint count 68 (TJC68), Swollen Joint Count 66 (SJC66), Participant's Assessment of Arthritis Pain, Participant's Global Assessment of Arthritis Disease Activity, Physician’s Global Assessment of Arthritis, CRP (mg/L) and Health Assessment Questionnaire – Disability Index (HAQ-DI). For all visits, if any of the component scores were missing, then those scores were considered as not having met the criteria for improvement.

End point type

Secondary

End point timeframe

Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[102]	37 ^[103]	37 ^[104]	37 ^[105]	37 ^[106]	37 ^[107]
Units: Percentage of participants
Week 1, ACR 20\|	0	5	8	11	5	19
Week 1, ACR 50\|	0	0	3	0	0	0
Week 1, ACR 70\|	0	0	0	0	0	0
Week 2, ACR 20\|	5	19	14	16	35	43
Week 2, ACR 50\|	0	3	3	8	5	5
Week 2, ACR 70\|	0	0	0	0	0	0
Week 4, ACR 20\|	8	24	35	32	46	46
Week 4, ACR 50\|	5	5	5	11	8	8
Week 4, ACR 70\|	0	0	0	3	0	5
Week 6, ACR 20\|	22	32	30	32	35	46
Week 6, ACR 50\|	11	5	8	11	14	14
Week 6, ACR 70\|	0	0	3	3	3	5
Week 8, ACR 20\|	16	24	41	46	49	51
Week 8, ACR 50\|	3	11	14	19	24	19
Week 8, ACR 70\|	3	0	3	11	8	8
Week 12, ACR 20\|	11	35	41	51	41	51
Week 12, ACR 50\|	8	11	27	24	30	22
Week 12, ACR 70\|	5	3	14	19	8	11
Week 16, ACR 20\|	16	30	46	51	41	68
Week 16, ACR 50\|	8	22	27	27	27	22
Week 16, ACR 70\|	5	3	14	19	11	11
Week 20, ACR 20\|	16	24	38	54	38	59
Week 20, ACR 50\|	8	11	24	22	32	30
Week 20, ACR 70\|	5	3	16	14	24	19
Week 24, ACR 20\|	14	24	41	57	41	59
Week 24, ACR 50\|	11	11	27	30	24	27
Week 24, ACR 70\|	5	5	14	14	19	19
Week 28, ACR 20\|	3	8	19	19	16	68
Week 28, ACR 50\|	3	8	16	19	16	24
Week 28, ACR 70\|	3	8	14	14	11	14
Week 32, ACR 20\|	3	8	22	22	16	54
Week 32, ACR 50\|	3	8	22	16	16	30
Week 32, ACR 70\|	3	5	19	14	14	16
Week 36, ACR 20\|	3	8	19	16	16	59
Week 36, ACR 50\|	3	5	19	11	16	35
Week 36, ACR 70\|	0	5	19	11	16	14
Week 40, ACR 20\|	3	8	19	22	16	54
Week 40, ACR 50\|	3	8	16	14	14	32
Week 40, ACR 70\|	3	5	16	14	11	16
Week 44, ACR 20\|	3	8	19	19	16	54
Week 44, ACR 50\|	3	8	19	16	14	38
Week 44, ACR 70\|	0	3	19	11	11	19
Week 48, ACR 20\|	3	8	19	19	16	57
Week 48, ACR 50\|	3	8	19	16	16	35
Week 48, ACR 70\|	0	5	19	8	14	22
Week 52, ACR 20\|	3	8	16	16	16	51
Week 52, ACR 50\|	3	8	16	16	16	27
Week 52, ACR 70\|	0	5	16	11	14	14
Week 62 (follow-up), ACR 20\|	3	8	16	11	16	43
Week 62 (follow-up), ACR 50\|	3	5	16	8	16	27
Week 62 (follow-up), ACR 70\|	3	0	16	3	14	19

Notes
[102] - ITT Population
[103] - ITT Population
[104] - ITT Population
[105] - ITT Population
[106] - ITT Population
[107] - ITT Population

Stat 1

Statistical analysis description

Week 1, ACR20. Difference to Placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 3

Statistical analysis description

Week 1, ACR20. Difference to Placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 2

Statistical analysis description

Week 1, ACR20. Difference to Placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 4

Statistical analysis description

Week 1, ACR50. Difference to Placebo for Week 1 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 5

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 6

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

21.3

Stat 7

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

24.7

Stat 8

Statistical analysis description

Week 2, ACR20. Difference to Placebo for 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 9

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 10

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 11

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

32.6

Stat 12

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.3

upper limit

44.7

Stat 13

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

6.9

upper limit

41.8

Stat 14

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

10.3

Stat 15

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

10.3

Stat 16

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

17.8

Stat 17

Statistical analysis description

Week 2, ACR20. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 18

Statistical analysis description

Week 6, ACR20. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

30.9

Stat 19

Statistical analysis description

Week 6, ACR20. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

27.9

Stat 20

Statistical analysis description

Week 6, ACR20. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

30.9

Stat 21

Statistical analysis description

Week 6, ACR50. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-17.8

upper limit

Stat 22

Statistical analysis description

Week 6, ACR50. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

10.6

Stat 23

Statistical analysis description

Week 6, ACR50. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

14.1

Stat 24

Statistical analysis description

Week 6, ACR70. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 25

Statistical analysis description

Week 6, ACR70. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 26

Statistical analysis description

Week 8, ACR20. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

26.3

Stat 27

Statistical analysis description

Week 8, ACR20. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

4.5

upper limit

44.1

Stat 28

Statistical analysis description

Week 8, ACR20. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

49.7

Stat 29

Statistical analysis description

Week 8, ACR50. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 30

Statistical analysis description

Week 8, ACR50. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 31

Statistical analysis description

Week 8, ACR50. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 32

Statistical analysis description

Week 8, ACR70. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 33

Statistical analysis description

Week 8, ACR70. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 34

Statistical analysis description

Week 8, ACR70. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 35

Statistical analysis description

Week 12, ACR20. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

42.7

Stat 36

Statistical analysis description

Week 12, ACR20. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Odds ratio (OR)

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

48.4

Stat 37

Statistical analysis description

Week 12, ACR20. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

40.5

Confidence interval

level

95%

sides

2-sided

lower limit

21.6

upper limit

59.5

Stat 38

Statistical analysis description

Week 12, ACR50. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-10.6

upper limit

Stat 39

Statistical analysis description

Week 12, ACR50. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

35.7

Stat 40

Statistical analysis description

Week 12, ACR50. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

32.6

Stat 41

Statistical analysis description

Week 12, ACR70. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

6.3

Stat 42

Statistical analysis description

Week 12, ACR70. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

21.3

Stat 43

Statistical analysis description

Week 12, ACR70. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 44

Statistical analysis description

Week 12, ACR20. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

32.4

Stat 45

Statistical analysis description

Week 16, ACR20. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

49.7

Stat 46

Statistical analysis description

Week 16, ACR20. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

35.1

Confidence interval

level

95%

sides

2-sided

lower limit

15.1

upper limit

55.1

Stat 47

Statistical analysis description

Week 16, ACR20. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

29.4

Stat 48

Statistical analysis description

Week 16, ACR50. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

35.7

Stat 49

Statistical analysis description

Week 16, ACR50. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

35.7

Stat 50

Statistical analysis description

Week 16, ACR70. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

6.3

Stat 51

Statistical analysis description

Week 16, ACR70. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

21.3

Stat 52

Statistical analysis description

Week 16, ACR70. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 53

Statistical analysis description

Week 20, ACR20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

26.3

Stat 54

Statistical analysis description

Week 20, ACR20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

41.2

Stat 55

Statistical analysis description

Week 20, ACR20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

17.9

upper limit

57.8

Stat 56

Statistical analysis description

Week 20, ACR50. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-10.6

upper limit

Stat 57

Statistical analysis description

Week 20, ACR50. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

32.6

Stat 58

Statistical analysis description

Week 20, ACR50. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

29.4

Stat 59

Statistical analysis description

Week 20, ACR70. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

6.3

Stat 60

Statistical analysis description

Week 20, ACR70. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

24.7

Stat 61

Statistical analysis description

Week 20, ACR70. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

21.3

Stat 62

Statistical analysis description

Week 24, ACR20. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

28.5

Stat 63

Statistical analysis description

Week 24, ACR20. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.7

upper limit

46.3

Stat 64

Statistical analysis description

Week 24, ACR20. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

43.2

Confidence interval

level

95%

sides

2-sided

lower limit

23.8

upper limit

62.6

Stat 65

Statistical analysis description

Week 24, ACR50. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

14.1

Stat 66

Statistical analysis description

Week 24, ACR50. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

33.7

Stat 67

Statistical analysis description

Week 24, ACR50. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

36.7

Stat 68

Statistical analysis description

Week 24, ACR70. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

10.3

Stat 69

Statistical analysis description

Week 24, ACR70. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

21.3

Stat 70

Statistical analysis description

Week 24, ACR70. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

21.3

Stat 71

Statistical analysis description

Week 28, ACR20. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 72

Statistical analysis description

Week 28, ACR20. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 73

Statistical analysis description

Week 28, ACR20. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 74

Statistical analysis description

Week 28, ACR50. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 75

Statistical analysis description

Week 28, ACR50. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 76

Statistical analysis description

Week 28, ACR50. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 77

Statistical analysis description

Week 28, ACR70. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 78

Statistical analysis description

Week 28, ACR70. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 79

Statistical analysis description

Week 28, ACR70. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 80

Statistical analysis description

Week 32, ACR20. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 81

Statistical analysis description

Week 32, ACR20. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 82

Statistical analysis description

Week 32, ACR20. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 83

Statistical analysis description

Week 32, ACR50. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 84

Statistical analysis description

Week 32, ACR50. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 85

Statistical analysis description

Week 32, ACR50. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 86

Statistical analysis description

Week 32, ACR70. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 87

Statistical analysis description

Week 32, ACR70. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 88

Statistical analysis description

Week 32, ACR70. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 89

Statistical analysis description

Week 36, ACR20. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 90

Statistical analysis description

Week 36, ACR20. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 91

Statistical analysis description

Week 36, ACR20. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 92

Statistical analysis description

Week 36, ACR50. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 93

Statistical analysis description

Week 36, ACR50. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 94

Statistical analysis description

Week 36, ACR50. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 95

Statistical analysis description

Week 36, ACR70. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 96

Statistical analysis description

Week 36, ACR70. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 97

Statistical analysis description

Week 36, ACR70 Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 98

Statistical analysis description

Week 40, ACR20 Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 99

Statistical analysis description

Week 40, ACR20 Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 100

Statistical analysis description

Week 40, ACR20. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

33.2

Stat 101

Statistical analysis description

Week 40, ACR50. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 102

Statistical analysis description

Week 40, ACR50. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 103

Statistical analysis description

Week 40, ACR50. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 104

Statistical analysis description

Week 40, ACR70. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 105

Statistical analysis description

Week 40, ACR70. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 106

Statistical analysis description

Week 40, ACR70. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 107

Statistical analysis description

Week 44, ACR20. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 108

Statistical analysis description

Week 44, ACR20. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 109

Statistical analysis description

Week 44, ACR20. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 110

Statistical analysis description

Week 44, ACR50. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 111

Statistical analysis description

Week 44, ACR50. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 112

Statistical analysis description

Week 44, ACR50. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 113

Statistical analysis description

Week 44, ACR70. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 114

Statistical analysis description

Week 44, ACR70. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 115

Statistical analysis description

Week 44, ACR70. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 116

Statistical analysis description

Week 48, ACR20 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 117

Statistical analysis description

Week 48, ACR20 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 118

Statistical analysis description

Week 48, ACR20 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 119

Statistical analysis description

Week 48, ACR50 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 120

Statistical analysis description

Week 48, ACR50 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 121

Statistical analysis description

Week 48, ACR50 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 122

Statistical analysis description

Week 48, ACR70 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 123

Statistical analysis description

Week 48, ACR70 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 124

Statistical analysis description

Week 48, ACR70 Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 125

Statistical analysis description

Week 52, ACR20 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 126

Statistical analysis description

Week 52, ACR20 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 127

Statistical analysis description

Week 52, ACR20 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 128

Statistical analysis description

Week 52, ACR50 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 129

Statistical analysis description

Week 52, ACR50 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 130

Statistical analysis description

Week 52, ACR50 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 131

Statistical analysis description

Week 52, ACR70 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 132

Statistical analysis description

Week 52, ACR70 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.3

upper limit

28.1

Stat 133

Statistical analysis description

Week 52, ACR70 Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 134

Statistical analysis description

Week 62 (follow-up), ACR20 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 135

Statistical analysis description

Week 62 (follow-up), ACR20 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 136

Statistical analysis description

Week 62 (follow-up), ACR20 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 137

Statistical analysis description

Week 62 (follow-up), ACR50 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 138

Statistical analysis description

Week 62 (follow-up), ACR50 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 139

Statistical analysis description

Week 62 (follow-up), ACR50 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 140

Statistical analysis description

Week 62 (follow-up), ACR70 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 141

Statistical analysis description

Week 62 (follow-up), ACR70 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 142

Statistical analysis description

Week 62 (follow-up), ACR70 Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 143

Statistical analysis description

Week 1, ACR20 Difference to Placebo is presented for Week 1. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 144

Statistical analysis description

Week 1, ACR20 Difference to Placebo is presented for Week 1. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 145

Statistical analysis description

Week 2, ACR20 Difference to Placebo is presented for Week 2. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

12.7

upper limit

46.8

Stat 146

Statistical analysis description

Week 2, ACR20 Difference to Placebo is presented for Week 2. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

20.3

upper limit

55.4

Stat 147

Statistical analysis description

Week 2, ACR50 Difference to Placebo is presented for Week 2. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 148

Statistical analysis description

Week 2, ACR50 Difference to Placebo is presented for Week 2. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 149

Statistical analysis description

Week 4, ACR20 Difference to Placebo is presented for Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

19.5

upper limit

56.1

Stat 150

Statistical analysis description

Week 4, ACR20 Difference to Placebo is presented for Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

19.5

upper limit

56.1

Stat 151

Statistical analysis description

Week 4, ACR50 Difference to Placebo is presented for Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

14.1

Stat 152

Statistical analysis description

Week 4, ACR50 Difference to Placebo is presented for Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

14.1

Stat 153

Statistical analysis description

Week 4, ACR70 Difference to Placebo is presented for Week 4. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 154

Statistical analysis description

Week 6, ACR20 Difference to Placebo is presented for Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

33.8

Stat 155

Statistical analysis description

Week 6, ACR20 Difference to Placebo is presented for Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

3.5

upper limit

45.2

Stat 156

Statistical analysis description

Week 6, ACR50 Difference to Placebo is presented for Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-12.2

upper limit

17.6

Stat 157

Statistical analysis description

Week 6, ACR50 Difference to Placebo is presented for Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-12.2

upper limit

17.6

Stat 158

Statistical analysis description

Week 6, ACR70 Difference to Placebo is presented for Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 159

Statistical analysis description

Week 6, ACR70 Difference to Placebo is presented for Week 6. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 160

Statistical analysis description

Week 8, ACR20 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

32.4

Confidence interval

level

95%

sides

2-sided

lower limit

12.4

upper limit

52.4

Stat 161

Statistical analysis description

Week 8, ACR20 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

35.1

Confidence interval

level

95%

sides

2-sided

lower limit

15.1

upper limit

55.1

Stat 163

Statistical analysis description

Week 8, ACR50 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Stat 162

Statistical analysis description

Week 8, ACR50 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

6.8

upper limit

36.4

Stat 164

Statistical analysis description

Week 8, ACR70 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 165

Statistical analysis description

Week 8, ACR70 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

15.6

Stat 166

Statistical analysis description

Week 12, ACR20 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

48.4

Stat 167

Statistical analysis description

Week 12, ACR20 Difference to Placebo is presented for Week 8. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

40.5

Confidence interval

level

95%

sides

2-sided

lower limit

21.6

upper limit

59.5

Stat 168

Statistical analysis description

Week 12, ACR50 Difference to Placebo is presented for Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

4.5

upper limit

38.8

Stat 169

Statistical analysis description

Week 12, ACR50 Difference to Placebo is presented for Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

29.4

Stat 170

Statistical analysis description

Week 12, ACR70 Difference to Placebo is presented for Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

14.1

Stat 172

Statistical analysis description

Week 16, ACR20 Difference to Placebo is presented for Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

4.5

upper limit

44.1

Stat 171

Statistical analysis description

Week 12, ACR70 Difference to Placebo is presented for Week 12. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

17.8

Stat 173

Statistical analysis description

Week 16, ACR20 Difference to Placebo is presented for Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

32.2

upper limit

70.5

Stat 174

Statistical analysis description

Week 16, ACR50 Difference to Placebo is presented for Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

35.7

Stat 175

Statistical analysis description

Week 16, ACR50 Difference to Placebo is presented for Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

29.4

Stat 176

Statistical analysis description

Week 16, ACR70 Difference to Placebo is presented for Week 16. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

17.8

Stat 178

Statistical analysis description

Week 20, ACR20 Difference to Placebo is presented for Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

43.2

Confidence interval

level

95%

sides

2-sided

lower limit

23.5

upper limit

Stat 177

Statistical analysis description

Week 20, ACR20 Difference to Placebo is presented for Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

41.2

Stat 179

Statistical analysis description

Week 20, ACR50 Difference to Placebo is presented for Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

6.9

upper limit

41.8

Stat 180

Statistical analysis description

Week 20, ACR50 Difference to Placebo is presented for Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

4.5

upper limit

38.8

Stat 181

Statistical analysis description

Week 20, ACR70 Difference to Placebo is presented for Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

3.3

upper limit

34.5

Stat 182

Statistical analysis description

Week 20, ACR70 Difference to Placebo is presented for Week 20. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 183

Statistical analysis description

Week 24, ACR20 Difference to Placebo is presented for Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.7

upper limit

46.3

Stat 184

Statistical analysis description

Week 24, ACR20 Difference to Placebo is presented for Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

45.9

Confidence interval

level

95%

sides

2-sided

lower limit

26.7

upper limit

65.2

Stat 185

Statistical analysis description

Week 24, ACR50 Difference to Placebo is presented for Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

30.6

Stat 186

Statistical analysis description

Week 24, ACR50 Difference to Placebo is presented for Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

33.7

Stat 187

Statistical analysis description

Week 24, ACR70 Difference to Placebo is presented for Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 188

Statistical analysis description

Week 24, ACR70 Difference to Placebo is presented for Week 24. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

28.1

Stat 189

Statistical analysis description

Week 28, ACR20 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 190

Statistical analysis description

Week 28, ACR20 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

64.9

Confidence interval

level

95%

sides

2-sided

lower limit

48.9

upper limit

80.8

Stat 191

Statistical analysis description

Week 28, ACR50 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 192

Statistical analysis description

Week 28, ACR50 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

6.8

upper limit

36.4

Stat 193

Statistical analysis description

Week 28, ACR70 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 194

Statistical analysis description

Week 28, ACR70 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 195

Statistical analysis description

Week 32, ACR20 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 196

Statistical analysis description

Week 32, ACR20 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

34.5

upper limit

68.2

Stat 197

Statistical analysis description

Week 32, ACR50 Difference to Placebo is presented for Week 28. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 198

Statistical analysis description

Week 32, ACR50 Difference to Placebo is presented for Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

11.4

upper limit

42.7

Stat 199

Statistical analysis description

Week 32, ACR70 Difference to Placebo is presented for Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 200

Statistical analysis description

Week 32, ACR70 Difference to Placebo is presented for Week 32. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 201

Statistical analysis description

Week 36, ACR20 Difference to Placebo is presented for Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 202

Statistical analysis description

Week 36, ACR20 Difference to Placebo is presented for Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

56.8

Confidence interval

level

95%

sides

2-sided

lower limit

40.1

upper limit

73.4

Stat 203

Statistical analysis description

Week 36, ACR50 Difference to Placebo is presented for Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 204

Statistical analysis description

Week 36, ACR50 Difference to Placebo is presented for Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

32.4

Confidence interval

level

95%

sides

2-sided

lower limit

16.2

upper limit

48.7

Stat 205

Statistical analysis description

Week 36, ACR70 Difference to Placebo is presented for Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.3

upper limit

28.1

Stat 206

Statistical analysis description

Week 36, ACR70 Difference to Placebo is presented for Week 36. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 207

Statistical analysis description

Week 40, ACR20 Difference to Placebo is presented for Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 208

Statistical analysis description

Week 40, ACR20 Difference to Placebo is presented for Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

34.5

upper limit

68.2

Stat 209

Statistical analysis description

Week 40, ACR50 Difference to Placebo is presented for Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 210

Statistical analysis description

Week 40, ACR50 Difference to Placebo is presented for Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

29.7

Confidence interval

level

95%

sides

2-sided

lower limit

13.8

upper limit

45.7

Stat 211

Statistical analysis description

Week 40, ACR70 Difference to Placebo is presented for Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 212

Statistical analysis description

Week 40, ACR70 Difference to Placebo is presented for Week 40. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 213

Statistical analysis description

Week 44, ACR20 Difference to Placebo is presented for Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 214

Statistical analysis description

Week 44, ACR20 Difference to Placebo is presented for Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

34.5

upper limit

68.2

Stat 215

Statistical analysis description

Week 44, ACR50 Difference to Placebo is presented for Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 216

Statistical analysis description

Week 44, ACR50 Difference to Placebo is presented for Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

35.1

Confidence interval

level

95%

sides

2-sided

lower limit

18.7

upper limit

51.6

Stat 217

Statistical analysis description

Week 44, ACR70 Difference to Placebo is presented for Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 218

Statistical analysis description

Week 44, ACR70 Difference to Placebo is presented for Week 44. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

31.5

Stat 219

Statistical analysis description

Week 48, ACR20 Difference to Placebo is presented for Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 220

Statistical analysis description

Week 48, ACR20 Difference to Placebo is presented for Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

37.3

upper limit

70.9

Stat 221

Statistical analysis description

Week 48, ACR50 Difference to Placebo is presented for Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 222

Statistical analysis description

Week 48, ACR50 Difference to Placebo is presented for Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

32.4

Confidence interval

level

95%

sides

2-sided

lower limit

16.2

upper limit

48.7

Stat 223

Statistical analysis description

Week 48, ACR70 Difference to Placebo is presented for Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 224

Statistical analysis description

Week 48, ACR70 Difference to Placebo is presented for Week 48. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

8.4

upper limit

34.9

Stat 225

Statistical analysis description

Week 52, ACR20 Difference to Placebo is presented for Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 226

Statistical analysis description

Week 52, ACR20 Difference to Placebo is presented for Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

48.6

Confidence interval

level

95%

sides

2-sided

lower limit

31.7

upper limit

65.6

Stat 227

Statistical analysis description

Week 52, ACR50 Difference to Placebo is presented for Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 228

Statistical analysis description

Week 52, ACR50 Difference to Placebo is presented for Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

9.1

upper limit

39.6

Stat 229

Statistical analysis description

Week 52, ACR70 Difference to Placebo is presented for Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 230

Statistical analysis description

Week 52, ACR70 Difference to Placebo is presented for Week 52. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 231

Statistical analysis description

Week 62 (follow-up), ACR20 Difference to Placebo is presented for Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 232

Statistical analysis description

Week 62 (follow-up), ACR20 Difference to Placebo is presented for Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

40.5

Confidence interval

level

95%

sides

2-sided

lower limit

23.7

upper limit

57.3

Stat 233

Statistical analysis description

Week 62 (follow-up), ACR50 Difference to Placebo is presented for Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

26.5

Stat 234

Statistical analysis description

Week 62 (follow-up), ACR50 Difference to Placebo is presented for Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

9.1

upper limit

39.6

Stat 235

Statistical analysis description

Week 62 (follow-up), ACR70 Difference to Placebo is presented for Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Stat 236

Statistical analysis description

Week 62 (follow-up), ACR70 Difference to Placebo is presented for Week 62 (follow-up). 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

29.9

Secondary: Percentage of participants with Index-based ACR/EULAR remission rates at all assessment time points

Top of page

End point title

Percentage of participants with Index-based ACR/EULAR remission rates at all assessment time points

End point description

Index-based remission was achieved if the following requirement was met: SDAI <= 3.3. If the SDAI value was missing at an individual assessment point, Index-based remission for that assessment was set to missing.

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[108]	37 ^[109]	37 ^[110]	37 ^[111]	37 ^[112]	37 ^[113]
Units: Percentage of participants
Index based ACR/EULAR, Week 1\|	0	0	0	0	0	0
Index based ACR/EULAR, Week 2\|	0	0	0	0	0	3
Index based ACR/EULAR, Week 4\|	0	0	0	3	0	3
Index based ACR/EULAR, Week 6\|	0	0	0	3	3	3
Index based ACR/EULAR, Week 8\|	3	0	0	3	3	3
Index based ACR/EULAR, Week 12\|	3	0	0	3	3	3
Index based ACR/EULAR, Week 16\|	0	0	3	14	3	5
Index based ACR/EULAR, Week 20\|	0	0	5	11	3	5
Index based ACR/EULAR, Week 24\|	0	0	5	8	8	5
Index based ACR/EULAR, Week 28\|	0	0	5	11	8	14
Index based ACR/EULAR, Week 32\|	0	0	14	8	8	11
Index based ACR/EULAR, Week 36\|	0	3	11	8	14	5
Index based ACR/EULAR, Week 40\|	0	3	11	8	5	14
Index based ACR/EULAR, Week 44\|	0	3	8	11	5	8
Index based ACR/EULAR, Week 48\|	0	3	11	8	11	3
Index based ACR/EULAR, Week 52\|	0	5	14	5	5	8
Index based ACR/EULAR, Week 62 (follow-up)\|	0	0	8	3	5	14

Notes
[108] - ITT Population
[109] - ITT Population
[110] - ITT Population
[111] - ITT Population
[112] - ITT Population
[113] - ITT Population

Stat 1

Statistical analysis description

Index based ACR/EULAR, Week 4. Difference to Placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 2

Statistical analysis description

Index based ACR/EULAR, Week 6. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 3

Statistical analysis description

Index based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 4

Statistical analysis description

Index based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 5

Statistical analysis description

Index based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 6

Statistical analysis description

Index based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 7

Statistical analysis description

Index based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 8

Statistical analysis description

Index based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 9

Statistical analysis description

Index based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 10

Statistical analysis description

Index based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 11

Statistical analysis description

Index based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 12

Statistical analysis description

Index based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 13

Statistical analysis description

Index based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 14

Statistical analysis description

Index based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 15

Statistical analysis description

Index based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 16

Statistical analysis description

Index based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 17

Statistical analysis description

Index based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 18

Statistical analysis description

Index based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 19

Statistical analysis description

Index based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 20

Statistical analysis description

Index based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 21

Statistical analysis description

Index based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 22

Statistical analysis description

Index based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 23

Statistical analysis description

Index based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 24

Statistical analysis description

Index based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 25

Statistical analysis description

Index based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 26

Statistical analysis description

Index based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 27

Statistical analysis description

Index based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 28

Statistical analysis description

Index based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 29

Statistical analysis description

Index based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 30

Statistical analysis description

Index based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 31

Statistical analysis description

Index based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 32

Statistical analysis description

Index based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 33

Statistical analysis description

Index based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 34

Statistical analysis description

Index based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 35

Statistical analysis description

Index based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 36

Statistical analysis description

Index based ACR/EULAR, Week 2. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 37

Statistical analysis description

Index based ACR/EULAR, Week 4. Difference to Placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 38

Statistical analysis description

Index based ACR/EULAR, Week 6. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 39

Statistical analysis description

Index based ACR/EULAR, Week 6. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 40

Statistical analysis description

Index based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 41

Statistical analysis description

Index based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 42

Statistical analysis description

Index based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 43

Statistical analysis description

Index based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 44

Statistical analysis description

Index based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 45

Statistical analysis description

Index based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 46

Statistical analysis description

Index based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

12.7

Stat 47

Statistical analysis description

Index based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

68.2

Stat 48

Statistical analysis description

Index based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 49

Statistical analysis description

Index based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 50

Statistical analysis description

Index based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 51

Statistical analysis description

Index based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 52

Statistical analysis description

Index based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 53

Statistical analysis description

Index based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 54

Statistical analysis description

Index based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 55

Statistical analysis description

Index based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 56

Statistical analysis description

Index based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 57

Statistical analysis description

Index based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 58

Statistical analysis description

Index based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 59

Statistical analysis description

Index based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 60

Statistical analysis description

Index based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 61

Statistical analysis description

Index based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 62

Statistical analysis description

Index based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 63

Statistical analysis description

Index based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 64

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 65

Statistical analysis description

Index based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Secondary: Percentage of participants with Boolean-based ACR/EULAR remission rates at all assessment time points

Top of page

End point title

Percentage of participants with Boolean-based ACR/EULAR remission rates at all assessment time points

End point description

Boolean-based remission was achieved if all of the following requirements were met at the same time: TJC68 <= 1,SJC66 <= 1,CRP <= 1mg/dL, PtGA <= 10. If one of the components was missing at an individual assessment point, Boolean-based remission for that assessment was set to missing.

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[114]	37 ^[115]	37 ^[116]	37 ^[117]	37 ^[118]	37 ^[119]
Units: Percentage of participants
Boolean based ACR/EULAR, Week 1\|	0	0	0	0	0	0
Boolean based ACR/EULAR, Week 2\|	0	0	0	0	0	3
Boolean based ACR/EULAR, Week 4\|	0	0	0	0	0	0
Boolean based ACR/EULAR, Week 6\|	0	0	0	0	3	3
Boolean based ACR/EULAR, Week 8\|	0	0	0	3	3	5
Boolean based ACR/EULAR, Week 12\|	0	0	0	8	0	3
Boolean based ACR/EULAR, Week 16\|	0	0	3	5	3	5
Boolean based ACR/EULAR, Week 20\|	0	0	5	8	3	5
Boolean based ACR/EULAR, Week 24\|	0	0	3	8	5	3
Boolean based ACR/EULAR, Week 28\|	0	0	5	8	5	5
Boolean based ACR/EULAR, Week 32\|	0	0	5	5	5	5
Boolean based ACR/EULAR, Week 36\|	0	0	8	5	8	3
Boolean based ACR/EULAR, Week 40\|	0	0	8	8	5	8
Boolean based ACR/EULAR, Week 44\|	0	0	11	8	5	5
Boolean based ACR/EULAR, Week 48\|	0	3	8	3	11	3
Boolean based ACR/EULAR, Week 52\|	0	0	11	3	5	5
Boolean based ACR/EULAR, Week 62 (follow-up)\|	0	0	8	3	3	5

Notes
[114] - ITT Population
[115] - ITT Population
[116] - ITT Population
[117] - ITT Population
[118] - ITT Population
[119] - ITT Population

Stat 1

Statistical analysis description

Boolean based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 2

Statistical analysis description

Boolean based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 3

Statistical analysis description

Boolean based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 4

Statistical analysis description

Boolean based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 5

Statistical analysis description

Boolean based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 6

Statistical analysis description

Boolean based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 7

Statistical analysis description

Boolean based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 8

Statistical analysis description

Boolean based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 9

Statistical analysis description

Boolean based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 10

Statistical analysis description

Boolean based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 11

Statistical analysis description

Boolean based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 13

Statistical analysis description

Boolean based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 12

Statistical analysis description

Boolean based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 14

Statistical analysis description

Boolean based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 15

Statistical analysis description

Boolean based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 16

Statistical analysis description

Boolean based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 17

Statistical analysis description

Boolean based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 18

Statistical analysis description

Boolean based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 19

Statistical analysis description

Boolean based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 20

Statistical analysis description

Boolean based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 21

Statistical analysis description

Boolean based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

21.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

42.8

Stat 22

Statistical analysis description

Boolean based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 23

Statistical analysis description

Boolean based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 24

Statistical analysis description

Boolean based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 25

Statistical analysis description

Boolean based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 26

Statistical analysis description

Boolean based ACR/EULAR, Week 2. Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 27

Statistical analysis description

Boolean based ACR/EULAR, Week 6. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 28

Statistical analysis description

Boolean based ACR/EULAR, Week 6. Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 29

Statistical analysis description

Boolean based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 30

Statistical analysis description

Boolean based ACR/EULAR, Week 8. Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 31

Statistical analysis description

Boolean based ACR/EULAR, Week 12. Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 32

Statistical analysis description

Boolean based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 33

Statistical analysis description

Boolean based ACR/EULAR, Week 16. Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 34

Statistical analysis description

Boolean based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 35

Statistical analysis description

Boolean based ACR/EULAR, Week 20. Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 36

Statistical analysis description

Boolean based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 37

Statistical analysis description

Boolean based ACR/EULAR, Week 24. Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 38

Statistical analysis description

Boolean based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 39

Statistical analysis description

Boolean based ACR/EULAR, Week 28. Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 40

Statistical analysis description

Boolean based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 41

Statistical analysis description

Boolean based ACR/EULAR, Week 32. Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 42

Statistical analysis description

Boolean based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 43

Statistical analysis description

Boolean based ACR/EULAR, Week 36. Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 44

Statistical analysis description

Boolean based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 45

Statistical analysis description

Boolean based ACR/EULAR, Week 40. Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 46

Statistical analysis description

Boolean based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 47

Statistical analysis description

Boolean based ACR/EULAR, Week 44. Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 48

Statistical analysis description

Boolean based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 49

Statistical analysis description

Boolean based ACR/EULAR, Week 48. Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 50

Statistical analysis description

Boolean based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 51

Statistical analysis description

Boolean based ACR/EULAR, Week 52. Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 52

Statistical analysis description

Boolean based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 53

Statistical analysis description

Boolean based ACR/EULAR, Week 62 (follow-up). Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Secondary: Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission

Top of page

End point title

Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission

End point description

CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC – Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Remission was achieved for a non-missing CDAI value <=2.8.

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[120]	37 ^[121]	37 ^[122]	37 ^[123]	37 ^[124]	37 ^[125]
Units: Percentage of participants
CDAI, Week 1\|	0	0	0	0	0	0
CDAI, Week 2\|	0	0	0	0	0	5
CDAI, Week 4\|	0	0	0	5	0	3
CDAI, Week 6\|	0	0	0	3	3	3
CDAI, Week 8\|	3	0	0	3	3	3
CDAI, Week 12\|	3	0	0	11	3	5
CDAI, Week 16\|	0	3	3	16	3	5
CDAI, Week 20\|	0	0	3	11	3	5
CDAI, Week 24\|	0	0	5	5	8	5
CDAI, Week 28\|	0	0	3	11	5	14
CDAI, Week 32\|	0	0	14	8	8	11
CDAI, Week 36\|	0	3	11	8	14	5
CDAI, Week 40\|	0	3	11	8	5	14
CDAI, Week 44\|	0	3	11	11	5	5
CDAI, Week 48\|	0	3	14	8	11	8
CDAI, Week 52\|	0	0	14	5	5	8
CDAI, Week 62 (follow-up)\|	0	0	8	3	5	16

Notes
[120] - ITT Population
[121] - ITT Population
[122] - ITT Population
[123] - ITT Population
[124] - ITT Population
[125] - ITT Population

Stat 1

Statistical analysis description

CDAI, Week 4, Difference to Placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 2

Statistical analysis description

CDAI, Week 6, Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 3

Statistical analysis description

CDAI, Week 8, Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 4

Statistical analysis description

CDAI, Week 8, Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 5

Statistical analysis description

CDAI, Week 8, Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 6

Statistical analysis description

CDAI, Week 12, Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 8

Statistical analysis description

CDAI, Week 12, Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

19.4

Stat 7

Statistical analysis description

CDAI, Week 12, Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

2.5

Stat 9

Statistical analysis description

CDAI, Week 16, Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 10

Statistical analysis description

CDAI, Week 16, Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 11

Statistical analysis description

CDAI, Week 16, Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.3

upper limit

28.1

Stat 12

Statistical analysis description

CDAI, Week 20, Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 13

Statistical analysis description

CDAI, Week 20, Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 14

Statistical analysis description

CDAI, Week 24, Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 15

Statistical analysis description

CDAI, Week 24, Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 16

Statistical analysis description

CDAI, Week 28, Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 17

Statistical analysis description

CDAI, Week 28, Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 18

Statistical analysis description

CDAI, Week 32, Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 19

Statistical analysis description

CDAI, Week 32, Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 20

Statistical analysis description

CDAI, Week 36, Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 21

Statistical analysis description

CDAI, Week 36, Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 22

Statistical analysis description

CDAI, Week 36, Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 23

Statistical analysis description

CDAI, Week 40, Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 24

Statistical analysis description

CDAI, Week 40, Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 25

Statistical analysis description

CDAI, Week 40, Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 26

Statistical analysis description

CDAI, Week 44, Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 27

Statistical analysis description

CDAI, Week 44, Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 28

Statistical analysis description

CDAI, Week 44, Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 29

Statistical analysis description

CDAI, Week 48, Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 30

Statistical analysis description

CDAI, Week 48, Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 31

Statistical analysis description

CDAI, Week 48, Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 32

Statistical analysis description

CDAI, Week 52, Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 34

Statistical analysis description

CDAI, Week 62 (follow up), Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 33

Statistical analysis description

CDAI, Week 52, Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 35

Statistical analysis description

CDAI, Week 62 (follow up), Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 36

Statistical analysis description

CDAI, Week 2, Difference to Placebo for Week 2 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 37

Statistical analysis description

CDAI, Week 4, Difference to Placebo for Week 4 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 38

Statistical analysis description

CDAI, Week 6, Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 39

Statistical analysis description

CDAI, Week 6, Difference to Placebo for Week 6 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 40

Statistical analysis description

CDAI, Week 8, Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 41

Statistical analysis description

CDAI, Week 8, Difference to Placebo for Week 8 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 42

Statistical analysis description

CDAI, Week 12, Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

7.4

Stat 43

Statistical analysis description

CDAI, Week 12, Difference to Placebo for Week 12 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

11.7

Stat 44

Statistical analysis description

CDAI, Week 16, Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 46

Statistical analysis description

CDAI, Week 20, Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

7.9

Stat 45

Statistical analysis description

CDAI, Week 16, Difference to Placebo for Week 16 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 47

Statistical analysis description

CDAI, Week 20, Difference to Placebo for Week 20 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 48

Statistical analysis description

CDAI, Week 24, Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 49

Statistical analysis description

CDAI, Week 24, Difference to Placebo for Week 24 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 50

Statistical analysis description

CDAI, Week 28, Difference to Placebo for Week 28 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 51

Statistical analysis description

CDAI, Week 32, Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 52

Statistical analysis description

CDAI, Week 32, Difference to Placebo for Week 32 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 53

Statistical analysis description

CDAI, Week 36, Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 54

Statistical analysis description

CDAI, Week 36, Difference to Placebo for Week 36 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 56

Statistical analysis description

CDAI, Week 40, Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

24.5

Stat 55

Statistical analysis description

CDAI, Week 40, Difference to Placebo for Week 40 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 57

Statistical analysis description

CDAI, Week 44, Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 58

Statistical analysis description

CDAI, Week 44, Difference to Placebo for Week 44 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 59

Statistical analysis description

CDAI, Week 48, Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

20.8

Stat 60

Statistical analysis description

CDAI, Week 48, Difference to Placebo for Week 48 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 61

Statistical analysis description

CDAI, Week 52, Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 63

Statistical analysis description

CDAI, Week 62 (follow-up), Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.7

Stat 62

Statistical analysis description

CDAI, Week 52, Difference to Placebo for Week 52 is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

16.9

Stat 64

Statistical analysis description

CDAI, Week 62 (follow-up), Difference to Placebo for Week 62 (follow-up) is presented. 95% CI were constructed using asymptotic Wald confidence limits without correction.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.3

upper limit

28.1

Secondary: Change from Baseline in SDAI at all assessment time points

Top of page

End point title

Change from Baseline in SDAI at all assessment time points

End point description

SDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician and acute phase reactants. SDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal-phalangeal I-V, proximal interphalangeal I-V and knees and calculated using the following formula: SDAI = TJC28+SJC28+GH+GP+CRP Where TJC-Tender joint Count, SJC=Swollen Joint Count, (GH=participant assessment, GP=physician assessment of disease activity), and CRP=C reactive Protein (in mg/L). It ranges between 0.1 and 86. High score (worse outcome), low score (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[126]	37 ^[127]	37 ^[128]	37 ^[129]	37 ^[130]	37 ^[131]
Units: Scores on a scale
least squares mean (standard error)
SDAI, Week 1,n=35,36,32,35, 34, 37\|	-1.53 ± 1.470	-5.62 ± 1.466	-5.20 ± 1.527	-5.86 ± 1.470	-6.31 ± 1.495	-9.30 ± 1.448
SDAI, Week 2,n=35,34,34,36,36,36\|	-4.56 ± 1.821	-8.62 ± 1.848	-9.28 ± 1.851	-10.03 ± 1.804	-11.22 ± 1.819	-11.40 ± 1.808
SDAI, Week 4,n=32,33,34,35, 36, 36\|	-5.53 ± 2.095	-12.30 ± 2.092	-12.81 ± 2.073	-14.76 ± 2.037	-13.97 ± 2.042	-18.03 ± 2.032
SDAI, Week 6,n=35,34,33,36,32, 36\|	-8.70 ± 2.132	-14.36 ± 2.152	-14.99 ± 2.163	-15.50 ± 2.095	-15.70 ± 2.165	-18.86 ± 2.109
SDAI, Week 8,n=34,33,34,37, 35, 32\|	-8.08 ± 2.349	-14.66 ± 2.367	-17.23 ± 2.353	-16.95 ± 2.281	-19.26 ± 2.329	-22.09 ± 2.358
SDAI, Week 12,n=34,35,33,37, 34, 36\|	-7.05 ± 2.729	-13.95 ± 2.712	-17.41 ± 2.741	-21.20 ± 2.640	-16.73 ± 2.708	-23.90 ± 2.676
SDAI, Week 16,n=8,16,20,23, 18, 36\|	-15.64 ± 3.222	-17.53 ± 2.707	-22.64 ± 2.605	-22.91 ± 2.484	-21.68 ± 2.632	-25.08 ± 2.351
SDAI, Week 20,n=8,15,20,25, 18, 35\|	-17.47 ± 3.523	-16.67 ± 2.835	-23.17 ± 2.621	-23.47 ± 2.437	-24.06 ± 2.670	-26.17 ± 2.263
SDAI, Week 24,n=8,14,20,24, 19, 33\|	-5.40 ± 4.484	-16.05 ± 3.569	-21.77 ± 3.165	-21.07 ± 2.945	-21.28 ± 3.200	-26.27 ± 2.667

Notes
[126] - ITT Population
[127] - ITT Population
[128] - ITT Population
[129] - ITT Population
[130] - ITT Population
[131] - ITT Population

Stat 1

Statistical analysis description

Week 1, SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.05 ^[132]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.09

Confidence interval

level

95%

sides

2-sided

lower limit

-8.18

upper limit

Notes
[132] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 1, SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.086 ^[133]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.66

Confidence interval

level

95%

sides

2-sided

lower limit

-7.84

upper limit

0.52

Notes
[133] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 1, SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.038 ^[134]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.33

Confidence interval

level

95%

sides

2-sided

lower limit

-8.43

upper limit

-0.23

Notes
[134] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 2, SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.119 ^[135]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.06

Confidence interval

level

95%

sides

2-sided

lower limit

-9.18

upper limit

1.05

Notes
[135] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 2, SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.071 ^[136]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.72

Confidence interval

level

95%

sides

2-sided

lower limit

-9.85

upper limit

0.4

Notes
[136] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 2, SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.034 ^[137]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.48

Confidence interval

level

95%

sides

2-sided

lower limit

-10.53

upper limit

-0.42

Notes
[137] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 4, SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.023 ^[138]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.78

Confidence interval

level

95%

sides

2-sided

lower limit

-12.61

upper limit

-0.94

Notes
[138] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 4, SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.014 ^[139]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.28

Confidence interval

level

95%

sides

2-sided

lower limit

-13.09

upper limit

-1.47

Notes
[139] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 4, SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002 ^[140]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.23

Confidence interval

level

95%

sides

2-sided

lower limit

-14.99

upper limit

-3.47

Notes
[140] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 6, SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.063 ^[141]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.65

Confidence interval

level

95%

sides

2-sided

lower limit

-11.62

upper limit

0.32

Notes
[141] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 6, SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.04 ^[142]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.29

Confidence interval

level

95%

sides

2-sided

lower limit

-12.28

upper limit

-0.3

Notes
[142] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 6, SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.024 ^[143]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.79

Confidence interval

level

95%

sides

2-sided

lower limit

-12.69

upper limit

-0.9

Notes
[143] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 8, SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.05 ^[144]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.58

Confidence interval

level

95%

sides

2-sided

lower limit

-13.15

upper limit

-0.01

Notes
[144] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 8, SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.006 ^[145]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.15

Confidence interval

level

95%

sides

2-sided

lower limit

-15.71

upper limit

-2.6

Notes
[145] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 8, SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007 ^[146]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.86

Confidence interval

level

95%

sides

2-sided

lower limit

-15.32

upper limit

-2.41

Notes
[146] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

Week 12, SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.074 ^[147]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.91

Confidence interval

level

95%

sides

2-sided

lower limit

-14.49

upper limit

0.68

Notes
[147] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

Week 12, SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.008 ^[148]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.37

Confidence interval

level

95%

sides

2-sided

lower limit

-17.99

upper limit

-2.74

Notes
[148] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

Week 12, SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[149]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-14.15

Confidence interval

level

95%

sides

2-sided

lower limit

-21.64

upper limit

-6.67

Notes
[149] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

Week 16,SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.656 ^[150]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.88

Confidence interval

level

95%

sides

2-sided

lower limit

-10.19

upper limit

6.43

Notes
[150] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

Week 16,SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.093 ^[151]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-15.19

upper limit

1.19

Notes
[151] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 21

Statistical analysis description

Week 16,SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.076 ^[152]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.26

Confidence interval

level

95%

sides

2-sided

lower limit

-15.3

upper limit

0.78

Notes
[152] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 22

Statistical analysis description

Week 20,SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.86 ^[153]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8.14

upper limit

9.74

Notes
[153] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 23

Statistical analysis description

Week 20,SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.196 ^[154]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.71

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

2.99

Notes
[154] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 24

Statistical analysis description

Week 20,SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.164 ^[155]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.48

upper limit

2.48

Notes
[155] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 25

Statistical analysis description

Week 24,SDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.066 ^[156]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.65

Confidence interval

level

95%

sides

2-sided

lower limit

-21.99

upper limit

0.69

Notes
[156] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 26

Statistical analysis description

Week 24,SDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003 ^[157]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-16.37

Confidence interval

level

95%

sides

2-sided

lower limit

-27.25

upper limit

-5.49

Notes
[157] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 27

Statistical analysis description

Week 24,SDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[158]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-15.67

Confidence interval

level

95%

sides

2-sided

lower limit

-26.3

upper limit

-5.03

Notes
[158] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 28

Statistical analysis description

Week 1,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.024 ^[159]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.78

Confidence interval

level

95%

sides

2-sided

lower limit

-8.91

upper limit

-0.65

Notes
[159] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 29

Statistical analysis description

Week 1,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[160]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.77

Confidence interval

level

95%

sides

2-sided

lower limit

-11.84

upper limit

-3.7

Notes
[160] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 30

Statistical analysis description

Week 2,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.01 ^[161]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.67

Confidence interval

level

95%

sides

2-sided

lower limit

-11.74

upper limit

-1.6

Notes
[161] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 31

Statistical analysis description

Week 2,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.008 ^[162]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.85

Confidence interval

level

95%

sides

2-sided

lower limit

-11.91

upper limit

-1.78

Notes
[162] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 32

Statistical analysis description

Week 4,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[163]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.44

Confidence interval

level

95%

sides

2-sided

lower limit

-14.2

upper limit

-2.67

Notes
[163] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 33

Statistical analysis description

Week 4,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[164]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.51

Confidence interval

level

95%

sides

2-sided

lower limit

-18.26

upper limit

-6.75

Notes
[164] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 34

Statistical analysis description

Week 6,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022 ^[165]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-12.99

upper limit

-1.01

Notes
[165] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 35

Statistical analysis description

Week 6,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[166]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.16

Confidence interval

level

95%

sides

2-sided

lower limit

-16.07

upper limit

-4.24

Notes
[166] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 36

Statistical analysis description

Week 8,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[167]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-11.18

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

-4.66

Notes
[167] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 37

Statistical analysis description

Week 8,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[168]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-14

Confidence interval

level

95%

sides

2-sided

lower limit

-20.57

upper limit

-7.44

Notes
[168] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 38

Statistical analysis description

Week 12,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.013 ^[169]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.68

Confidence interval

level

95%

sides

2-sided

lower limit

-17.26

upper limit

-2.11

Notes
[169] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 39

Statistical analysis description

Week 12,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[170]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-16.86

Confidence interval

level

95%

sides

2-sided

lower limit

-24.39

upper limit

-9.32

Notes
[170] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 40

Statistical analysis description

Week 16,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.149 ^[171]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.03

Confidence interval

level

95%

sides

2-sided

lower limit

-14.24

upper limit

2.18

Notes
[171] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 41

Statistical analysis description

Week 16,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.019 ^[172]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.43

Confidence interval

level

95%

sides

2-sided

lower limit

-17.32

upper limit

-1.55

Notes
[172] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 42

Statistical analysis description

Week 20,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.138 ^[173]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.59

Confidence interval

level

95%

sides

2-sided

lower limit

-15.32

upper limit

2.14

Notes
[173] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 43

Statistical analysis description

Week 20,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.04 ^[174]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-16.99

upper limit

-0.42

Notes
[174] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 44

Statistical analysis description

Week 24,SDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[175]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-15.88

Confidence interval

level

95%

sides

2-sided

lower limit

-26.77

upper limit

-4.98

Notes
[175] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 45

Statistical analysis description

Week 24,SDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[176]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-20.87

Confidence interval

level

95%

sides

2-sided

lower limit

-31.2

upper limit

-10.53

Notes
[176] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Change from Baseline in CDAI at all assessment time points

Top of page

End point title

Change from Baseline in CDAI at all assessment time points

End point description

CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC – Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[177]	37 ^[178]	37 ^[179]	37 ^[180]	37 ^[181]	37 ^[182]
Units: Scores on a scale
least squares mean (standard error)
CDAI, Week 1, n=36,36,33,36, 35, 37\|	-1.34 ± 1.449	-5.18 ± 1.455	-5.18 ± 1.497	-5.76 ± 1.448	-5.23 ± 1.469	-8.73 ± 1.438
CDAI, Week 2,n=35,34,36,37, 36, 37\|	-4.25 ± 1.782	-8.42 ± 1.807	-7.72 ± 1.771	-9.45 ± 1.752	-10.35 ± 1.777	-11.10 ± 1.755
CDAI, Week 4,n=33,33,35,36, 36, 36\|	-4.95 ± 2.013	-12.15 ± 2.024	-11.68 ± 1.978	-14.15 ± 1.958	-12.88 ± 1.974	-17.14 ± 1.965
CDAI, Week 6,n=35,35,33,37, 34, 36\|	-8.20 ± 2.089	-13.68 ± 2.094	-14.05 ± 2.101	-14.83 ± 2.042	-13.82 ± 2.094	-18.37 ± 2.065
CDAI, Week 8,n=34,33,35,37, 35, 34\|	-7.57 ± 2.298	-13.98 ± 2.315	-16.17 ± 2.270	-16.31 ± 2.232	-17.94 ± 2.276	-21.36 ± 2.279
CDAI, Week 12,n=34,35,35,37, 35, 36\|	-6.59 ± 2.658	-13.40 ± 2.640	-16.39 ± 2.621	-20.47 ± 2.571	-16.26 ± 2.625	-23.23 ± 2.604
CDAI, Week 16,n=8,16,21,23, 18, 36\|	-15.61 ± 3.077	-17.30 ± 2.586	-21.94 ± 2.445	-22.05 ± 2.371	-21.14 ± 2.508	-24.47 ± 2.245
CDAI, Week 20,n=8,15,21,25, 18, 35\|	-16.91 ± 3.419	-15.87 ± 2.730	-22.31 ± 2.470	-22.81 ± 2.334	-23.46 ± 2.564	-25.58 ± 2.158
CDAI, Week 24,n=8,14,21,24, 19, 33\|	-5.77 ± 4.267	-15.14 ± 3.389	-20.88 ± 2.947	-20.67 ± 2.791	-21.19 ± 3.037	-25.65 ± 2.529

Notes
[177] - ITT Population
[178] - ITT Population
[179] - ITT Population
[180] - ITT Population
[181] - ITT Population
[182] - ITT Population

Stat 1

Statistical analysis description

Week 1,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.063 ^[183]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.84

Confidence interval

level

95%

sides

2-sided

lower limit

-7.89

upper limit

0.2

Notes
[183] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 1,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.067 ^[184]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.84

Confidence interval

level

95%

sides

2-sided

lower limit

-7.95

upper limit

0.28

Notes
[184] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 1,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.032 ^[185]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.43

Confidence interval

level

95%

sides

2-sided

lower limit

-8.46

upper limit

-0.39

Notes
[185] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 2,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.102 ^[186]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.17

Confidence interval

level

95%

sides

2-sided

lower limit

-9.17

upper limit

0.84

Notes
[186] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 2,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.17 ^[187]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.47

Confidence interval

level

95%

sides

2-sided

lower limit

-8.43

upper limit

1.49

Notes
[187] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 2,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.039 ^[188]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.13

upper limit

-0.27

Notes
[188] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 4,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.012 ^[189]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.2

Confidence interval

level

95%

sides

2-sided

lower limit

-12.82

upper limit

-1.57

Notes
[189] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 4,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.018 ^[190]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.73

Confidence interval

level

95%

sides

2-sided

lower limit

-12.3

upper limit

-1.16

Notes
[190] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 4,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[191]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.19

Confidence interval

level

95%

sides

2-sided

lower limit

-14.73

upper limit

-3.66

Notes
[191] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 6,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.065 ^[192]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.48

Confidence interval

level

95%

sides

2-sided

lower limit

-11.31

upper limit

0.35

Notes
[192] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 6,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.05 ^[193]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.85

Confidence interval

level

95%

sides

2-sided

lower limit

-11.69

upper limit

Notes
[193] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 6,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.024 ^[194]

Method

MMRM

Parameter type

Mean difference (final values)

Point estimate

-6.63

Confidence interval

level

95%

sides

2-sided

lower limit

-12.38

upper limit

-0.87

Notes
[194] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 8,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.051 ^[195]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.41

Confidence interval

level

95%

sides

2-sided

lower limit

-12.84

upper limit

0.02

Notes
[195] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 8,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.008 ^[196]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.97

upper limit

-2.22

Notes
[196] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 8,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007 ^[197]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.74

Confidence interval

level

95%

sides

2-sided

lower limit

-15.06

upper limit

-2.43

Notes
[197] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

Week 12,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.071 ^[198]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.8

Confidence interval

level

95%

sides

2-sided

lower limit

-14.19

upper limit

0.58

Notes
[198] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

Week 12,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.009 ^[199]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.8

Confidence interval

level

95%

sides

2-sided

lower limit

-17.17

upper limit

-2.44

Notes
[199] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

Week 12,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[200]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.88

Confidence interval

level

95%

sides

2-sided

lower limit

-21.17

upper limit

-6.59

Notes
[200] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

Week 16,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.676 ^[201]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.68

Confidence interval

level

95%

sides

2-sided

lower limit

-9.63

upper limit

6.26

Notes
[201] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

Week 16,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.11 ^[202]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.33

Confidence interval

level

95%

sides

2-sided

lower limit

-14.11

upper limit

1.44

Notes
[202] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 21

Statistical analysis description

Week 16,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.099 ^[203]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.44

Confidence interval

level

95%

sides

2-sided

lower limit

-14.12

upper limit

1.23

Notes
[203] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 22

Statistical analysis description

Week 20,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.812 ^[204]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

-7.61

upper limit

9.69

Notes
[204] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 23

Statistical analysis description

Week 20,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.204 ^[205]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.39

Confidence interval

level

95%

sides

2-sided

lower limit

-13.75

upper limit

2.96

Notes
[205] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 24

Statistical analysis description

Week 20,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.157 ^[206]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-14.09

upper limit

2.3

Notes
[206] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 25

Statistical analysis description

Week 24,CDAI

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.088 ^[207]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.37

Confidence interval

level

95%

sides

2-sided

lower limit

-20.15

upper limit

1.42

Notes
[207] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 26

Statistical analysis description

Week 24,CDAI

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[208]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-15.12

Confidence interval

level

95%

sides

2-sided

lower limit

-25.4

upper limit

-4.83

Notes
[208] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 27

Statistical analysis description

Week 24,CDAI

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[209]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-14.91

Confidence interval

level

95%

sides

2-sided

lower limit

-25.01

upper limit

-4.8

Notes
[209] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 28

Statistical analysis description

Week 1,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.06 ^[210]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.89

Confidence interval

level

95%

sides

2-sided

lower limit

-7.96

upper limit

0.17

Notes
[210] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 29

Statistical analysis description

Week 1,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[211]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.39

Confidence interval

level

95%

sides

2-sided

lower limit

-11.42

upper limit

-3.36

Notes
[211] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 30

Statistical analysis description

Week 2,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.016 ^[212]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.1

Confidence interval

level

95%

sides

2-sided

lower limit

-11.06

upper limit

-1.14

Notes
[212] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 31

Statistical analysis description

Week 2,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007 ^[213]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.85

Confidence interval

level

95%

sides

2-sided

lower limit

-11.78

upper limit

-1.91

Notes
[213] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 32

Statistical analysis description

Week 4,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[214]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.92

Confidence interval

level

95%

sides

2-sided

lower limit

-13.48

upper limit

-2.37

Notes
[214] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 33

Statistical analysis description

Week 4,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[215]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.19

Confidence interval

level

95%

sides

2-sided

lower limit

-17.74

upper limit

-6.64

Notes
[215] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 34

Statistical analysis description

Week 6,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.059 ^[216]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.62

Confidence interval

level

95%

sides

2-sided

lower limit

-11.45

upper limit

0.21

Notes
[216] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 35

Statistical analysis description

Week 6,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[217]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.17

Confidence interval

level

95%

sides

2-sided

lower limit

-15.97

upper limit

-4.38

Notes
[217] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 36

Statistical analysis description

Week 8,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002 ^[218]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.37

Confidence interval

level

95%

sides

2-sided

lower limit

-16.75

upper limit

-4

Notes
[218] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 37

Statistical analysis description

Week 8,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[219]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.79

Confidence interval

level

95%

sides

2-sided

lower limit

-20.18

upper limit

-7.41

Notes
[219] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 38

Statistical analysis description

Week 12,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.01 ^[220]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.67

Confidence interval

level

95%

sides

2-sided

lower limit

-17.03

upper limit

-2.31

Notes
[220] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 39

Statistical analysis description

Week 12,CDAI

Comparison groups

GSK3196165 180 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[221]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-16.63

Confidence interval

level

95%

sides

2-sided

lower limit

-23.97

upper limit

-9.3

Notes
[221] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 40

Statistical analysis description

Week 16,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.165 ^[222]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.53

Confidence interval

level

95%

sides

2-sided

lower limit

-13.37

upper limit

2.3

Notes
[222] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 41

Statistical analysis description

Week 16,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022 ^[223]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.85

Confidence interval

level

95%

sides

2-sided

lower limit

-16.39

upper limit

-1.32

Notes
[223] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 42

Statistical analysis description

Week 20,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.127 ^[224]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.55

Confidence interval

level

95%

sides

2-sided

lower limit

-14.99

upper limit

1.89

Notes
[224] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 43

Statistical analysis description

Week 20,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.034 ^[225]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.67

Confidence interval

level

95%

sides

2-sided

lower limit

-16.67

upper limit

-0.67

Notes
[225] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 44

Statistical analysis description

Week 24,CDAI

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[226]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-15.43

Confidence interval

level

95%

sides

2-sided

lower limit

-25.78

upper limit

-5.07

Notes
[226] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 45

Statistical analysis description

Week 24,CDAI

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[227]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-19.88

Confidence interval

level

95%

sides

2-sided

lower limit

-29.7

upper limit

-10.06

Notes
[227] - MMRM analysis adjusted for CDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Change from Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) at all assessment time points

Top of page

End point title

Change from Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) at all assessment time points

End point description

HAQ-DI is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas; dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each functional area contains at least 2 questions. For each question, there is a 4level response set that is scored ranging from 0 (without any difficulty) to 3 (unable to do). If aids/devices/physical assistance are used for a specific functional area and the maximum response of this functional area is 0/1 the according value is increased to a score of 2. HAQ-DI is only calculated if at least 6 functional area scores available. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[228]	37 ^[229]	37 ^[230]	37 ^[231]	37 ^[232]	37 ^[233]
Units: Scores on a scale
least squares mean (standard error)
HAQ-DI, Week 1,n=36,36,35,36, 36, 37\|	-0.09 ± 0.054	-0.08 ± 0.054	-0.08 ± 0.054	-0.10 ± 0.054	-0.13 ± 0.054	-0.17 ± 0.053
HAQ-DI, Week 2,n=36,35,37,37, 36, 37\|	-0.17 ± 0.062	-0.13 ± 0.063	-0.16 ± 0.062	-0.23 ± 0.062	-0.25 ± 0.063	-0.26 ± 0.062
HAQ-DI, Week 4,n=34,34,36,37, 36, 36\|	-0.22 ± 0.073	-0.18 ± 0.073	-0.17 ± 0.072	-0.29 ± 0.071	-0.29 ± 0.072	-0.40 ± 0.072
HAQ-DI, Week 6,n=35,35,35,37, 36, 36\|	-0.23 ± 0.077	-0.22 ± 0.077	-0.27 ± 0.077	-0.33 ± 0.076	-0.21 ± 0.077	-0.43 ± 0.076
HAQ-DI, Week 8,n=34,34,35,37, 35, 34\|	-0.22 ± 0.082	-0.18 ± 0.082	-0.33 ± 0.081	-0.31 ± 0.080	-0.35 ± 0.081	-0.42 ± 0.081
HAQ-DI, Week 12,n=34,35, 35, 37,35, 36\|	-0.26 ± 0.091	-0.31 ± 0.091	-0.30 ± 0.090	-0.37 ± 0.89	-0.38 ± 0.090	-0.50 ± 0.090
HAQ-DI, Week 16,n=8,16,21,24, 18, 36\|	-0.49 ± 0.141	-0.33 ± 0.111	-0.38 ± 0.102	-0.57 ± 0.098	-0.40 ± 0.106	-0.50 ± 0.090
HAQ-DI, Week 20,n=8,15,21,25, 19, 36\|	-0.35 ± 0.139	-0.37 ± 0.112	-0.42 ± 0.103	-0.51 ± 0.097	-0.49 ± 0.105	-0.56 ± 0.091
HAQ-DI, Week 24,n=8,14,21,24, 19, 34\|	-0.34 ± 0.143	-0.32 ± 0.116	-0.41 ± 0.104	-0.43 ± 0.099	-0.42 ± 0.107	-0.54 ± 0.092

Notes
[228] - ITT Population
[229] - ITT Population
[230] - ITT Population
[231] - ITT Population
[232] - ITT Population
[233] - ITT Population

Stat 1

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.938 ^[234]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.16

Notes
[234] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.981 ^[235]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

0.15

Notes
[235] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.857 ^[236]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.14

Notes
[236] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.592 ^[237]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.22

Notes
[237] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.917 ^[238]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.18

Notes
[238] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.545 ^[239]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.12

Notes
[239] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.707 ^[240]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.24

Notes
[240] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.603 ^[241]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

0.26

Notes
[241] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.473 ^[242]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.13

Notes
[242] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.987 ^[243]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.22

Notes
[243] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.713 ^[244]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.17

Notes
[244] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.357 ^[245]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

0.11

Notes
[245] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.748 ^[246]

Method

MMRM

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.26

Notes
[246] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.327 ^[247]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.11

Notes
[247] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.395 ^[248]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.13

Notes
[248] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.71 ^[249]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.21

Notes
[249] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.74 ^[250]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.21

Notes
[250] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.398 ^[251]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.14

Notes
[251] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.364 ^[252]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.52

Notes
[252] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.503 ^[253]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.46

Notes
[253] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 21

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.647 ^[254]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.26

Notes
[254] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 22

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.91 ^[255]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.33

Notes
[255] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 23

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.66 ^[256]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.26

Notes
[256] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 24

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.34 ^[257]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.17

Notes
[257] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 25

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.902 ^[258]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.39

Notes
[258] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 26

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.687 ^[259]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.28

Notes
[259] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 27

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.599 ^[260]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

0.25

Notes
[260] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 28

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.588 ^[261]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.11

Notes
[261] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 29

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.259 ^[262]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.06

Notes
[262] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 30

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.358 ^[263]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.09

Notes
[263] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 31

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.325 ^[264]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.09

Notes
[264] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 32

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.473 ^[265]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.13

Notes
[265] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 33

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.085 ^[266]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.02

Notes
[266] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 34

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.897 ^[267]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.23

Notes
[267] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 35

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.065 ^[268]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.01

Notes
[268] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 36

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.238 ^[269]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.09

Notes
[269] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 37

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.071 ^[270]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

0.02

Notes
[270] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 38

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.34 ^[271]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.13

Notes
[271] - MMRM analysis adjusted for SDAI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 39

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.059 ^[272]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.49

upper limit

0.01

Notes
[272] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 40

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.607 ^[273]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.44

Notes
[273] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 41

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.959 ^[274]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.32

Notes
[274] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 42

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.401 ^[275]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.49

upper limit

0.2

Notes
[275] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 43

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.207 ^[276]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

0.12

Notes
[276] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 44

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.637 ^[277]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

0.27

Notes
[277] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 45

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.251 ^[278]

Method

MMRM

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.53

upper limit

0.14

Notes
[278] - MMRM analysis adjusted for HAQ-DI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Change from Baseline in pain score at all assessment time points

Top of page

End point title

Change from Baseline in pain score at all assessment time points

End point description

Participants assessed the severity of their current arthritis pain using a 100 unit visual analog scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37	37	37	37	37	37
Units: Scores on a scale
least squares mean (standard error)
Week 1,n=36,36,35,36, 36,37\|	-2.25 ± 2.625	-4.71 ± 2.648	-5.02 ± 2.656	-9.96 ± 2.626	-7.18 ± 2.637	-7.89 ± 2.619
Week 2,n=36,35,37,37,36,37\|	-3.79 ± 2.818	-6.71 ± 2.870	-9.77 ± 2.797	-11.37 ± 2.791	-11.63 ± 2.829	-14.22 ± 2.810
Week 4,n=34,34,36,37, 36,36\|	-5.44 ± 3.081	-8.47 ± 3.107	-14.83 ± 3.029	-17.65 ± 2.995	-13.39 ± 3.036	-19.40 ± 3.038
Week 6,n=35,35,35,37, 36, 36\|	-6.69 ± 3.334	-11.18 ± 3.357	-14.71 ± 3.319	-15.05 ± 3.262	-14.05 ± 3.306	-19.12 ± 3.311
Week 8,n=34,34,35,37, 35,34\|	-3.98 ± 3.555	-9.60 ± 3.577	-18.55 ± 3.517	-17.92 ± 3.461	-20.49 ± 3.523	-24.38 ± 3.541
Week 12,n=34,35,35,37, 35, 36\|	-7.07 ± 3.705	-14.09 ± 3.702	-21.22 ± 3.659	-25.25 ± 3.593	-19.07 ± 3.662	-25.01 ± 3.650
Week 16,n=8,16,21,24, 18, 16\|	-12.60 ± 6.077	-17.50 ± 4.768	-28.56 ± 4.361	-26.46 ± 4.187	-25.80 ± 4.549	-24.48 ± 3.807
Week 20,n=8,15,21,25, 19,36\|	-13.95 ± 5.589	-14.64 ± 4.495	-27.12 ± 4.068	-27.44 ± 3.870	-27.86 ± 4.179	-27.17 ± 3.584
Week 24,n=8,14,21,24, 19, 34\|	-13.38 ± 6.484	-19.76 ± 5.231	-23.52 ± 4.620	-25.45 ± 4.409	-26.61 ± 4.756	-30.08 ± 4.048

Stat 1

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.511 ^[279]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.45

Confidence interval

level

95%

sides

2-sided

lower limit

-9.81

upper limit

4.9

Notes
[279] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.461 ^[280]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.76

Confidence interval

level

95%

sides

2-sided

lower limit

-10.13

upper limit

4.6

Notes
[280] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.039 ^[281]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.71

Confidence interval

level

95%

sides

2-sided

lower limit

-15.03

upper limit

-0.39

Notes
[281] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.469 ^[282]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.92

Confidence interval

level

95%

sides

2-sided

lower limit

-10.86

upper limit

5.01

Notes
[282] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.133 ^[283]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.99

Confidence interval

level

95%

sides

2-sided

lower limit

-13.82

upper limit

1.85

Notes
[283] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.057 ^[284]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.58

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

0.23

Notes
[284] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.49 ^[285]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.03

Confidence interval

level

95%

sides

2-sided

lower limit

-11.67

upper limit

5.61

Notes
[285] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.031 ^[286]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.38

Confidence interval

level

95%

sides

2-sided

lower limit

-17.91

upper limit

-0.86

Notes
[286] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[287]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.21

Confidence interval

level

95%

sides

2-sided

lower limit

-20.67

upper limit

-3.74

Notes
[287] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.345 ^[288]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.49

Confidence interval

level

95%

sides

2-sided

lower limit

-13.83

upper limit

4.85

Notes
[288] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.09 ^[289]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.02

Confidence interval

level

95%

sides

2-sided

lower limit

-17.3

upper limit

1.26

Notes
[289] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.074 ^[290]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-8.36

Confidence interval

level

95%

sides

2-sided

lower limit

-17.55

upper limit

0.83

Notes
[290] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.268 ^[291]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.61

Confidence interval

level

95%

sides

2-sided

lower limit

-15.57

upper limit

4.34

Notes
[291] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[292]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-14.57

Confidence interval

level

95%

sides

2-sided

lower limit

-24.43

upper limit

-4.7

Notes
[292] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[293]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.94

Confidence interval

level

95%

sides

2-sided

lower limit

-23.72

upper limit

-4.16

Notes
[293] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.182 ^[294]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.02

Confidence interval

level

95%

sides

2-sided

lower limit

-17.36

upper limit

3.32

Notes
[294] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.007 ^[295]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-14.15

Confidence interval

level

95%

sides

2-sided

lower limit

-24.42

upper limit

-3.87

Notes
[295] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[296]

Method

MMRM

Parameter type

Mean difference (final values)

Point estimate

-18.18

Confidence interval

level

95%

sides

2-sided

lower limit

-28.35

upper limit

-8.01

Notes
[296] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.527 ^[297]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.89

Confidence interval

level

95%

sides

2-sided

lower limit

-20.15

upper limit

10.36

Notes
[297] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.034 ^[298]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-15.95

Confidence interval

level

95%

sides

2-sided

lower limit

-30.72

upper limit

-1.19

Notes
[298] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 21

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.062 ^[299]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.86

Confidence interval

level

95%

sides

2-sided

lower limit

-28.42

upper limit

0.7

Notes
[299] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 22

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.924 ^[300]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-14.85

upper limit

13.47

Notes
[300] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 23

Statistical analysis description

Week 20

Comparison groups

GSK3196165 45 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.058 ^[301]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.17

Confidence interval

level

95%

sides

2-sided

lower limit

-26.82

upper limit

0.48

Notes
[301] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 24

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.049 ^[302]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.49

Confidence interval

level

95%

sides

2-sided

lower limit

-26.91

upper limit

-0.08

Notes
[302] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 25

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.445 ^[303]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-6.38

Confidence interval

level

95%

sides

2-sided

lower limit

-22.84

upper limit

10.07

Notes
[303] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 26

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.205 ^[304]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.14

Confidence interval

level

95%

sides

2-sided

lower limit

-25.87

upper limit

5.58

Notes
[304] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 27

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.125 ^[305]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.07

Confidence interval

level

95%

sides

2-sided

lower limit

-27.55

upper limit

3.41

Notes
[305] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 28

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.187 ^[306]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.93

Confidence interval

level

95%

sides

2-sided

lower limit

-12.26

upper limit

2.41

Notes
[306] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 29

Statistical analysis description

Week 1

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.13 ^[307]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.63

Confidence interval

level

95%

sides

2-sided

lower limit

-12.93

upper limit

1.67

Notes
[307] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 30

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.051 ^[308]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.85

Confidence interval

level

95%

sides

2-sided

lower limit

-15.72

upper limit

0.03

Notes
[308] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 31

Statistical analysis description

Week 2

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.009 ^[309]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-10.44

Confidence interval

level

95%

sides

2-sided

lower limit

-18.27

upper limit

-2.6

Notes
[309] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 32

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.068 ^[310]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.94

Confidence interval

level

95%

sides

2-sided

lower limit

-16.47

upper limit

0.58

Notes
[310] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 33

Statistical analysis description

Week 4

Comparison groups

GSK3196165 180 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[311]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.96

Confidence interval

level

95%

sides

2-sided

lower limit

-22.47

upper limit

-5.44

Notes
[311] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 34

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.118 ^[312]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-7.36

Confidence interval

level

95%

sides

2-sided

lower limit

-16.62

upper limit

1.89

Notes
[312] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 35

Statistical analysis description

Week 6

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.009 ^[313]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.43

Confidence interval

level

95%

sides

2-sided

lower limit

-21.68

upper limit

-3.19

Notes
[313] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 36

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[314]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-16.51

Confidence interval

level

95%

sides

2-sided

lower limit

-26.38

upper limit

-6.65

Notes
[314] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 37

Statistical analysis description

Week 8

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[315]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-20.39

Confidence interval

level

95%

sides

2-sided

lower limit

-30.27

upper limit

-10.52

Notes
[315] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 38

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022 ^[316]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12

Confidence interval

level

95%

sides

2-sided

lower limit

-22.27

upper limit

-1.73

Notes
[316] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 39

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[317]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-17.94

Confidence interval

level

95%

sides

2-sided

lower limit

-28.18

upper limit

-7.7

Notes
[317] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 40

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.084 ^[318]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-28.18

upper limit

1.79

Notes
[318] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 41

Statistical analysis description

Week 16

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.099 ^[319]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-11.87

Confidence interval

level

95%

sides

2-sided

lower limit

-26.02

upper limit

2.27

Notes
[319] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 42

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.048 ^[320]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.91

Confidence interval

level

95%

sides

2-sided

lower limit

-27.68

upper limit

-0.14

Notes
[320] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 43

Statistical analysis description

Week 20

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.048 ^[321]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.22

Confidence interval

level

95%

sides

2-sided

lower limit

-26.32

upper limit

-0.13

Notes
[321] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 44

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.102 ^[322]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.23

Confidence interval

level

95%

sides

2-sided

lower limit

-29.11

upper limit

2.64

Notes
[322] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 45

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.03 ^[323]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-16.7

Confidence interval

level

95%

sides

2-sided

lower limit

-31.79

upper limit

-1.62

Notes
[323] - MMRM analysis adjusted for Pain Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Change from Baseline in physical and mental component scores (PCS, MCS) and in domain scores of short form 36 (SF-36) at all assessment time points

Top of page

End point title

Change from Baseline in physical and mental component scores (PCS, MCS) and in domain scores of short form 36 (SF-36) at all assessment time points

End point description

SF-36 (generic health survey) yields an 8-scale profile of functional health and well-being scores as well as PCS and MCS health summary scores. The version 2, 1-week recall questionnaire was used. Recoding, calculations and standardization were done as per the User’s manual of SF-36. All raw domain scores were transformed on a 0–100 scale (transformed domain scores) and then standardized into norm-based scores using Z-score. Following the transformation of the 8 domain scores into z-scores, the MCS and PCS were aggregated (AGG) using weights as PCS/MCS=50+(AGG_PHYS *10/AGG_MENT *10). High score (worse outcome) and low score (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 4, 12, 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[324]	37 ^[325]	37 ^[326]	37 ^[327]	37 ^[328]	37 ^[329]
Units: Scores on a scale
least squares mean (standard error)
PCS, Week 4,n=34,34,36,37,36,36,\|	1.86 ± 1.046	2.46 ± 1.048	5.05 ± 1.020	4.47 ± 1.007	4.80 ± 1.021	5.97 ± 1.028
PCS Week 12,n=34,35,35,37,35,36\|	3.42 ± 1.203	4.88 ± 1.192	5.84 ± 1.186	5.15 ± 1.158	5.31 ± 1.188	6.97 ± 1.182
PCS, Week 24,n=8,14,21,24,19,34\|	5.34 ± 2.058	7.03 ± 1.631	6.63 ± 1.404	7.80 ± 1.335	7.50 ± 1.454	6.99 ± 1.211
MCS, Week 4,n=34,34,36,37,36,36,\|	3.36 ± 1.488	2.86 ± 1.488	3.81 ± 1.453	2.82 ± 1.434	4.52 ± 1.453	3.46 ± 1.453
MCS, Week 12,n=34,35,35,37,35,36,\|	3.54 ± 1.558	4.86 ± 1.542	5.00 ± 1.535	4.66 ± 1.501	5.51 ± 1.535	6.79 ± 1.521
MCS, Week 24,n=8,14,21,24,19,34\|	4.07 ± 2.560	4.50 ± 2.039	6.36 ± 1.755	3.02 ± 1.669	5.42 ± 1.817	7.86 ± 1.503
Bodily pain, Week 4,n=34,34,36,37,36,36,\|	2.52 ± 1.071	2.41 ± 1.071	6.24 ± 1.043	5.44 ± 1.029	5.97 ± 1.046	7.60 ± 1.045
Bodily pain, Week 12,n=34,35,35,37,35,36\|	3.90 ± 1.294	5.43 ± 1.280	6.72 ± 1.273	5.99 ± 1.243	6.01 ± 1.277	7.34 ± 1.263
Bodily pain, Week 24,n=8,14,21,24,19,34\|	4.15 ± 2.580	7.01 ± 1.996	9.20 ± 1.682	7.36 ± 1.593	8.87 ± 1.752	9.35 ± 1.387
General Health, Week 4,n=34,34,36,37,36,36\|	1.78 ± 1.079	1.27 ± 1.079	2.77 ± 1.055	1.90 ± 1.039	3.43 ± 1.053	3.72 ± 1.054
General health, Week 12,n=34,35,35,37,35,36\|	2.44 ± 1.102	3.07 ± 1.090	4.30 ± 1.088	3.02 ± 1.061	3.14 ± 1.087	4.73 ± 1.077
General health, Week 24,n=8,14,21,24,19,34\|	2.07 ± 2.248	5.36 ± 1.762	4.83 ± 1.514	4.60 ± 1.420	3.84 ± 1.562	5.42 ± 1.265
Mental health, Week 4,n=34,34,36,37,36,36\|	3.64 ± 1.451	3.77 ± 1.449	4.52 ± 1.413	3.62 ± 1.395	3.49 ± 1.413	3.69 ± 1.413
Mental health, Week 12,n=34,35,35,37,35,36\|	2.27 ± 1.601	4.87 ± 1.581	5.49 ± 1.575	4.77 ± 1.539	4.68 ± 1.576	5.72 ± 1.558
Mental health, Week 24,n=8,14,21,24,19,34\|	2.81 ± 2.619	4.13 ± 2.073	6.09 ± 1.777	3.42 ± 1.684	4.96 ± 1.844	7.82 ± 1.504
Physical functioning, Week 4,n=34,34,36,37,36,36\|	3.30 ± 1.206	3.97 ± 1.208	5.68 ± 1.174	4.84 ± 1.159	5.18 ± 1.179	5.75 ± 1.180
Physical functioning, Week 12,n=34,35,35,37,35,36\|	2.98 ± 1.390	5.80 ± 1.375	5.99 ± 1.368	5.98 ± 1.333	5.84 ± 1.373	7.76 ± 1.358
Physical functioning, Week 24,n=8,14,21,24,19,34\|	6.93 ± 2.100	6.29 ± 1.700	6.52 ± 1.490	7.16 ± 1.426	7.40 ± 1.539	7.58 ± 1.309
Role emotional, Week 4,n=34,34,36,37,36,36\|	4.37 ± 1.489	3.09 ± 1.488	3.08 ± 1.452	3.35 ± 1.432	4.96 ± 1.451	3.77 ± 1.451
Role emotional, Week 12,n=34,35,35,37,35,36\|	4.85 ± 1.595	5.19 ± 1.574	5.52 ± 1.570	5.10 ± 1.532	5.93 ± 1.570	7.54 ± 1.552
Role emotional, Week 24,n=8,14,21,24,19,34\|	5.66 ± 2.674	6.57 ± 2.102	6.16 ± 1.794	4.36 ± 1.704	6.06 ± 1.863	8.18 ± 1.518
Role physical, Week 4,n=34,34,36,37,36,36\|	2.15 ± 1.128	3.01 ± 1.124	4.04 ± 1.097	4.56 ± 1.082	4.02 ± 1.097	4.80 ± 1.099
Role physical, Week 12,n=34,35,35,37,35,36\|	4.56 ± 1.270	5.16 ± 1.255	6.28 ± 1.251	5.49 ± 1.221	5.99 ± 1.253	7.91 ± 1.241
Role physical, Week 24,n=8,14,21,24,19,34\|	6.38 ± 2.235	7.65 ± 1.738	6.27 ± 1.481	7.50 ± 1.408	7.59 ± 1.538	7.25 ± 1.250
Social functioning, Week 4,n=34,34,36,37,36,36\|	2.27 ± 1.512	1.95 ± 1.512	5.44 ± 1.475	2.84 ± 1.455	5.22 ± 1.476	5.67 ± 1.475
Social functioning, Week 12,n=34,35,35,37,35,36\|	4.34 ± 1.529	4.90 ± 1.513	4.34 ± 1.507	4.62 ± 1.471	6.32 ± 1.508	8.69 ± 1.491
Social functioning, Week 24,n=8,14,21,24,19,34\|	8.31 ± 2.841	5.41 ± 2.221	7.87 ± 1.871	4.52 ± 1.773	7.97 ± 1.951	8.60 ± 1.551
Vitality, Week 4,n=34,34,36,37,36,36\|	1.91 ± 1.389	2.94 ± 1.386	5.48 ± 1.352	4.54 ± 1.334	6.55 ± 1.352	5.25 ± 1.353
Vitality, Week 12,n=34,35,35,37,35,36\|	4.19 ± 1.445	6.16 ± 1.429	7.10 ± 1.421	6.37 ± 1.389	6.83 ± 1.421	8.16 ± 1.408
Vitality, Week 24,n=8,14,21,24,19,34\|	4.68 ± 2.775	6.62 ± 2.175	7.83 ± 1.854	7.65 ± 1.758	8.04 ± 1.924	7.81 ± 1.560

Notes
[324] - ITT Population
[325] - ITT Population
[326] - ITT Population
[327] - ITT Population
[328] - ITT Population
[329] - ITT Population

Stat 1

Statistical analysis description

Week 4, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.683 ^[330]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

3.52

Notes
[330] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 4, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.03 ^[331]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

6.07

Notes
[331] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 4, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.074 ^[332]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

5.47

Notes
[332] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 12, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.39 ^[333]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

-1.88

upper limit

4.8

Notes
[333] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 12, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.154 ^[334]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

5.75

Notes
[334] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 12, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.302 ^[335]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

5.02

Notes
[335] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 24, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.521 ^[336]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

6.88

Notes
[336] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 24, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.606 ^[337]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

-3.63

upper limit

6.2

Notes
[337] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 24, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.32 ^[338]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.46

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

7.32

Notes
[338] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 4, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.811 ^[339]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.65

upper limit

3.64

Notes
[339] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 4, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.83 ^[340]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-3.65

upper limit

4.55

Notes
[340] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 4, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.795 ^[341]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-4.61

upper limit

3.54

Notes
[341] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 12, , MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.548 ^[342]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

5.64

Notes
[342] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 12, , MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.505 ^[343]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

-2.85

upper limit

5.77

Notes
[343] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 12, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.605 ^[344]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-3.15

upper limit

5.39

Notes
[344] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 16

Statistical analysis description

Week 24, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.895 ^[345]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-6.03

upper limit

6.9

Notes
[345] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 17

Statistical analysis description

Week 24, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.461 ^[346]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.29

Confidence interval

level

95%

sides

2-sided

lower limit

-3.84

upper limit

8.42

Notes
[346] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 18

Statistical analysis description

Week 24, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.732 ^[347]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.05

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

4.99

Notes
[347] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 19

Statistical analysis description

Week 4, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.941 ^[348]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-3.11

upper limit

2.88

Notes
[348] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 20

Statistical analysis description

Week 4, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.013 ^[349]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

6.67

Notes
[349] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 21

Statistical analysis description

Week 4, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.051 ^[350]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.92

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

5.84

Notes
[350] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 22

Statistical analysis description

Week 12, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.403 ^[351]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

5.12

Notes
[351] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 23

Statistical analysis description

Week 12, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.122 ^[352]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

6.4

Notes
[352] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 24

Statistical analysis description

Week 12, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.247 ^[353]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

-1.45

upper limit

5.62

Notes
[353] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 25

Statistical analysis description

Week 24, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.384 ^[354]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

-3.61

upper limit

9.32

Notes
[354] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 26

Statistical analysis description

Week 24, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.105 ^[355]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

5.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

11.16

Notes
[355] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 27

Statistical analysis description

Week 24, Bodily Pain MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.29 ^[356]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.21

Confidence interval

level

95%

sides

2-sided

lower limit

-2.76

upper limit

9.17

Notes
[356] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 28

Statistical analysis description

Week 4, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.738 ^[357]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-3.52

upper limit

2.5

Notes
[357] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 29

Statistical analysis description

Week 4, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.513 ^[358]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-1.99

upper limit

3.97

Notes
[358] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 30

Statistical analysis description

Week 4, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.934 ^[359]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-2.83

upper limit

3.08

Notes
[359] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 31

Statistical analysis description

Week 12, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.687 ^[360]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-2.43

upper limit

3.68

Notes
[360] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 32

Statistical analysis description

Week 12, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.233 ^[361]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

4.91

Notes
[361] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 33

Statistical analysis description

Week 12, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.708 ^[362]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-2.44

upper limit

3.59

Notes
[362] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 34

Statistical analysis description

Week 24, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.25 ^[363]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.29

Confidence interval

level

95%

sides

2-sided

lower limit

-2.34

upper limit

8.93

Notes
[363] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 35

Statistical analysis description

Week 24, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.307 ^[364]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.57

upper limit

8.09

Notes
[364] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 36

Statistical analysis description

Week 24, General Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.345 ^[365]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.74

upper limit

7.79

Notes
[365] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 37

Statistical analysis description

Week 4, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.95 ^[366]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.52

Notes
[366] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 38

Statistical analysis description

Week 4, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.664 ^[367]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-3.11

upper limit

4.87

Notes
[367] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 39

Statistical analysis description

Week 4, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.994 ^[368]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-3.99

upper limit

3.96

Notes
[368] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 40

Statistical analysis description

Week 12, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.25 ^[369]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.84

upper limit

7.03

Notes
[369] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 41

Statistical analysis description

Week 12, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.154 ^[370]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

7.64

Notes
[370] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 42

Statistical analysis description

Week 12, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.262 ^[371]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.88

upper limit

6.89

Notes
[371] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 43

Statistical analysis description

Week 24, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.693 ^[372]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-5.28

upper limit

7.93

Notes
[372] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 44

Statistical analysis description

Week 24, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.302 ^[373]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.28

Confidence interval

level

95%

sides

2-sided

lower limit

-2.98

upper limit

9.54

Notes
[373] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 45

Statistical analysis description

Week 24, Mental Health MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.844 ^[374]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-5.54

upper limit

6.77

Notes
[374] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 46

Statistical analysis description

Week 4, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.698 ^[375]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-2.71

upper limit

4.04

Notes
[375] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 47

Statistical analysis description

Week 4, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.159 ^[376]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

5.7

Notes
[376] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 48

Statistical analysis description

Week 4, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.36 ^[377]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

-1.76

upper limit

4.83

Notes
[377] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 49

Statistical analysis description

Week 12, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.151 ^[378]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

6.69

Notes
[378] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 50

Statistical analysis description

Week 12, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.124 ^[379]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

6.86

Notes
[379] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 51

Statistical analysis description

Week 12, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.12 ^[380]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.79

upper limit

6.8

Notes
[380] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 52

Statistical analysis description

Week 24, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.814 ^[381]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-5.98

upper limit

4.7

Notes
[381] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 53

Statistical analysis description

Week 24, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.873 ^[382]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-5.49

upper limit

4.67

Notes
[382] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 54

Statistical analysis description

Week 24, Physical Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.928 ^[383]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

5.26

Notes
[383] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 55

Statistical analysis description

Week 4, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.541 ^[384]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-5.44

upper limit

2.86

Notes
[384] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 56

Statistical analysis description

Week 4, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.535 ^[385]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-5.39

upper limit

2.81

Notes
[385] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 57

Statistical analysis description

Week 4, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.62 ^[386]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

3.05

Notes
[386] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 58

Statistical analysis description

Week 12, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.881 ^[387]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-4.08

upper limit

4.76

Notes
[387] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 59

Statistical analysis description

Week 12,Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.767 ^[388]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-3.74

upper limit

5.07

Notes
[388] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 60

Statistical analysis description

Week 12, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.913 ^[389]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-4.12

upper limit

4.61

Notes
[389] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 61

Statistical analysis description

Week 24, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.79 ^[390]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

-5.81

upper limit

7.63

Notes
[390] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 62

Statistical analysis description

Week 24, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.876 ^[391]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.86

upper limit

6.87

Notes
[391] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 63

Statistical analysis description

Week 24, Role Emotional MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.684 ^[392]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.59

upper limit

4.99

Notes
[392] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 64

Statistical analysis description

Week 4, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.588 ^[393]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

-2.28

upper limit

4.01

Notes
[393] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 65

Statistical analysis description

Week 4, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.229 ^[394]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.21

upper limit

Notes
[394] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 66

Statistical analysis description

Week 4, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.125 ^[395]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

5.49

Notes
[395] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 67

Statistical analysis description

Week 12, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.736 ^[396]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.92

upper limit

4.12

Notes
[396] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 68

Statistical analysis description

Week 12, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.338 ^[397]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

5.23

Notes
[397] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 69

Statistical analysis description

Week 12, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.6 ^[398]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

-2.55

upper limit

4.4

Notes
[398] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 70

Statistical analysis description

Week 24, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.657 ^[399]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-4.34

upper limit

6.86

Notes
[399] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 71

Statistical analysis description

Week 24, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.965 ^[400]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-5.41

upper limit

5.17

Notes
[400] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 72

Statistical analysis description

Week 24, Role Physical MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.675 ^[401]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.14

upper limit

6.37

Notes
[401] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 73

Statistical analysis description

Week 4, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.88 ^[402]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-4.54

upper limit

3.89

Notes
[402] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 74

Statistical analysis description

Week 4, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.135 ^[403]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.17

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

7.33

Notes
[403] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 75

Statistical analysis description

Week 4, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.785 ^[404]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-3.56

upper limit

4.71

Notes
[404] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 76

Statistical analysis description

Week 12, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.797 ^[405]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-3.69

upper limit

4.8

Notes
[405] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 77

Statistical analysis description

Week 12, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

> 0.999 ^[406]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.23

upper limit

4.23

Notes
[406] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 78

Statistical analysis description

Week 12, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.896 ^[407]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-3.91

upper limit

4.46

Notes
[407] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 79

Statistical analysis description

Week 24, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.424 ^[408]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.89

Confidence interval

level

95%

sides

2-sided

lower limit

-10.02

upper limit

4.24

Notes
[408] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 80

Statistical analysis description

Week 24, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.898 ^[409]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-7.16

upper limit

6.29

Notes
[409] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 81

Statistical analysis description

Week 24, Social Functioning MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.26 ^[410]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.79

Confidence interval

level

95%

sides

2-sided

lower limit

-10.42

upper limit

2.84

Notes
[410] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 82

Statistical analysis description

Week 4, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.603 ^[411]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

-2.85

upper limit

4.9

Notes
[411] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 83

Statistical analysis description

Week 4, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.068 ^[412]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.56

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

7.39

Notes
[412] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 84

Statistical analysis description

Week 4, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.174 ^[413]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.17

upper limit

6.43

Notes
[413] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 85

Statistical analysis description

Week 12, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.334 ^[414]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.04

upper limit

5.98

Notes
[414] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 86

Statistical analysis description

Week 12, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.153 ^[415]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.91

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

6.91

Notes
[415] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 87

Statistical analysis description

Week 12, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.279 ^[416]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

-1.78

upper limit

6.13

Notes
[416] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 88

Statistical analysis description

Week 24,Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.584 ^[417]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

-5.04

upper limit

8.91

Notes
[417] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 89

Statistical analysis description

Week 24, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.346 ^[418]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.15

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

9.73

Notes
[418] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 90

Statistical analysis description

Week 24, Vitality MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.37 ^[419]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.97

Confidence interval

level

95%

sides

2-sided

lower limit

-3.55

upper limit

9.48

Notes
[419] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 91

Statistical analysis description

Week 4, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.045 ^[420]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

5.83

Notes
[420] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 92

Statistical analysis description

Week 4, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.006 ^[421]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

4.11

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

7.01

Notes
[421] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 93

Statistical analysis description

Week 12,PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.264 ^[422]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.89

Confidence interval

level

95%

sides

2-sided

lower limit

-1.44

upper limit

5.23

Notes
[422] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 94

Statistical analysis description

Week 12,PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.037 ^[423]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

6.88

Notes
[423] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 95

Statistical analysis description

Week 24, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.392 ^[424]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.81

upper limit

7.14

Notes
[424] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 96

Statistical analysis description

Week 24, PCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.493 ^[425]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

-3.09

upper limit

6.39

Notes
[425] - MMRM analysis adjusted for PCS Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 97

Statistical analysis description

Week 4, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.577 ^[426]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.94

upper limit

5.26

Notes
[426] - MMRM analysis adjusted for MCS Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 98

Statistical analysis description

Week 4, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.964 ^[427]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.01

upper limit

4.2

Notes
[427] - MMRM analysis adjusted for MCS Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 99

Statistical analysis description

Week 12, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.37 ^[428]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.35

upper limit

6.28

Notes
[428] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 100

Statistical analysis description

Week 12, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.138 ^[429]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.25

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

7.54

Notes
[429] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 101

Statistical analysis description

Week 24, MCS MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.667 ^[430]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

-4.85

upper limit

7.56

Notes
[430] - MMRM analysis adjusted for Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 102

Statistical analysis description

Week 24, MCS MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.203 ^[431]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.79

Confidence interval

level

95%

sides

2-sided

lower limit

-4.85

upper limit

7.56

Notes
[431] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions.

Stat 103

Statistical analysis description

Week 4, Bodily pain MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.023 ^[432]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

6.41

Notes
[432] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 104

Statistical analysis description

Week 4, Bodily pain MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[433]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

5.08

Confidence interval

level

95%

sides

2-sided

lower limit

2.14

upper limit

8.03

Notes
[433] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 105

Statistical analysis description

Week 12, Bodily pain MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.249 ^[434]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-1.49

upper limit

5.7

Notes
[434] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 106

Statistical analysis description

Week 12, Bodily pain MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.059 ^[435]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.43

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

6.99

Notes
[435] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 107

Statistical analysis description

Week 24, Bodily pain MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.134 ^[436]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

4.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

10.9

Notes
[436] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 108

Statistical analysis description

Week 24, Bodily pain MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.078 ^[437]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

10.97

Notes
[437] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 109

Statistical analysis description

Week 4, General health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.275 ^[438]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.32

upper limit

4.62

Notes
[438] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 110

Statistical analysis description

Week 4, General health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.199 ^[439]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

4.91

Notes
[439] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 111

Statistical analysis description

Week 12, General health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.654 ^[440]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-2.36

upper limit

3.74

Notes
[440] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 112

Statistical analysis description

Week 12, General health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.138 ^[441]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

5.33

Notes
[441] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 113

Statistical analysis description

Week 24, General health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.516 ^[442]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

-3.62

upper limit

7.17

Notes
[442] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 114

Statistical analysis description

Week 24, General health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.198 ^[443]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.35

Confidence interval

level

95%

sides

2-sided

lower limit

-1.77

upper limit

8.46

Notes
[443] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 115

Statistical analysis description

Week 4, Mental health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.941 ^[444]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-4.15

upper limit

3.84

Notes
[444] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 116

Statistical analysis description

Week 4, Mental health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.979 ^[445]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-3.94

upper limit

4.05

Notes
[445] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 117

Statistical analysis description

Week 12, Mental health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.287 ^[446]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.03

upper limit

6.84

Notes
[446] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 118

Statistical analysis description

Week 12, Mental health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.125 ^[447]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

7.85

Notes
[447] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 119

Statistical analysis description

Week 24, Mental health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.503 ^[448]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.15

Confidence interval

level

95%

sides

2-sided

lower limit

-4.18

upper limit

8.49

Notes
[448] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 120

Statistical analysis description

Week 24,Mental health MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.099 ^[449]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

5.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

10.98

Notes
[449] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 121

Statistical analysis description

Week 4, Physical functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.268 ^[450]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.88

Confidence interval

level

95%

sides

2-sided

lower limit

-1.45

upper limit

5.21

Notes
[450] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 122

Statistical analysis description

Week 4, Physical functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.147 ^[451]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

5.77

Notes
[451] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 123

Statistical analysis description

Week 12, Physical functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.145 ^[452]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.87

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

6.73

Notes
[452] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 124

Statistical analysis description

Week 12, Physical functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.014 ^[453]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

4.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

8.61

Notes
[453] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 125

Statistical analysis description

Week 24, Physical functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.856 ^[454]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-4.66

upper limit

5.61

Notes
[454] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 126

Statistical analysis description

Week 24, Physical functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.793 ^[455]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-4.24

upper limit

5.55

Notes
[455] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 127

Statistical analysis description

Week 4, Role emotional MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.778 ^[456]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-3.51

upper limit

4.69

Notes
[456] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 128

Statistical analysis description

Week 4, Role emotional MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.773 ^[457]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

3.5

Notes
[457] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 129

Statistical analysis description

Week 12, Role emotional MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.631 ^[458]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-3.34

upper limit

5.49

Notes
[458] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 130

Statistical analysis description

Week 12, Role emotional MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.23 ^[459]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.71

upper limit

7.07

Notes
[459] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 131

Statistical analysis description

Week 24, Role emotional MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.901 ^[460]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-6.03

upper limit

6.84

Notes
[460] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 132

Statistical analysis description

Week 24, Role emotional MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.412 ^[461]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.52

Confidence interval

level

95%

sides

2-sided

lower limit

-3.54

upper limit

8.59

Notes
[461] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 133

Statistical analysis description

Week 4, Role physical MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.234 ^[462]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.88

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

4.98

Notes
[462] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 134

Statistical analysis description

Week 4, Role physical MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.094 ^[463]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.66

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

5.77

Notes
[463] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 135

Statistical analysis description

Week 12, Role physical MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.423 ^[464]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

4.94

Notes
[464] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 136

Statistical analysis description

Week 12, Role physical MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.061 ^[465]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

6.86

Notes
[465] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 137

Statistical analysis description

Week 24, Role physical MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.657 ^[466]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

-4.16

upper limit

6.57

Notes
[466] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 138

Statistical analysis description

Week 24, Role physical MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.737 ^[467]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-4.22

upper limit

5.95

Notes
[467] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 139

Statistical analysis description

Week 4, Social Functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.165 ^[468]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.95

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

7.11

Notes
[468] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 140

Statistical analysis description

Week 4, Social Functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.109 ^[469]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

7.56

Notes
[469] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 141

Statistical analysis description

Week 12, Social Functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.359 ^[470]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.26

upper limit

6.21

Notes
[470] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 142

Statistical analysis description

Week 12, Social Functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.043 ^[471]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

4.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

8.56

Notes
[471] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 143

Statistical analysis description

Week 24, Social Functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.923 ^[472]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-7.15

upper limit

6.49

Notes
[472] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 144

Statistical analysis description

Week 24, Social Functioning MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.927 ^[473]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.11

upper limit

6.7

Notes
[473] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions.

Stat 145

Statistical analysis description

Week 4, Vitality MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.018 ^[474]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

4.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

8.46

Notes
[474] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions.

Stat 146

Statistical analysis description

Week 4, Vitality MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.087 ^[475]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.49

upper limit

7.17

Notes
[475] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 147

Statistical analysis description

Week 12, Vitality MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.193 ^[476]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

6.64

Notes
[476] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 148

Statistical analysis description

Week 12, Vitality MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.051 ^[477]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.97

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

7.95

Notes
[477] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 149

Statistical analysis description

Week 24, Vitality MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.321 ^[478]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.36

Confidence interval

level

95%

sides

2-sided

lower limit

-3.31

upper limit

10.02

Notes
[478] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions

Stat 150

Statistical analysis description

Week 24, Vitality MMRM analysis adjusted for baseline, treatment group, visit, treatment group by visit and baseline by visit interactions.

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.328 ^[479]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.13

Confidence interval

level

95%

sides

2-sided

lower limit

-3.18

upper limit

9.44

Notes
[479] - MMRM analysis adjusted for Baseline, treatment group, visit, treatment group by visit and Baseline by visit interactions.

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at all assessment time points

Top of page

End point title

Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at all assessment time points

End point description

FACIT-fatigue questionnaire is a participant reported measure developed to assess fatigue consisting of 13 statements using a numeric rating scale ranging from 0 to 4. For only 2 of the items (i.e. Answer 5 [An5] and An7) a higher value represents a lower fatigue; 11 of the item scores (i.e. HI7, HI12, An1, An2, An3, An4, An8, An12, An14, An15, An16) have to be reversed by subtracting the captured value from 4 (0 is turned to a 4; 1 into 3; 3 into 1; 4 into 0). The final score ranges from 0 to 52 with higher values representing a lower fatigue (better quality of life). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 4, 12, 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[480]	37 ^[481]	37 ^[482]	37 ^[483]	37 ^[484]	37 ^[485]
Units: Scores on a scale
least squares mean (standard error)
Week 4,n=34,34,36,37, 36, 36\|	3.16 ± 1.192	2.51 ± 1.191	4.66 ± 1.164	5.71 ± 1.148	6.73 ± 1.165	5.97 ± 1.165
Week 12,n=34,35,35,37, 35, 36\|	3.37 ± 1.291	5.29 ± 1.278	5.91 ± 1.273	6.44 ± 1.244	7.28 ± 1.274	8.70 ± 1.262
Week 24,n=8,14,21,24, 19, 34\|	7.56 ± 2.439	8.31 ± 1.946	7.09 ± 1.680	6.74 ± 1.595	8.28 ± 1.737	9.43 ± 1.443

Notes
[480] - ITT Population.
[481] - ITT Population.
[482] - ITT Population.
[483] - ITT Population.
[484] - ITT Population.
[485] - ITT Population.

Stat 1

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.701 ^[486]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-3.97

upper limit

2.67

Notes
[486] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.37 ^[487]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.79

upper limit

4.78

Notes
[487] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.125 ^[488]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

5.81

Notes
[488] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.292 ^[489]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

5.5

Notes
[489] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.163 ^[490]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.54

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

6.11

Notes
[490] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.087 ^[491]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

6.61

Notes
[491] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.808 ^[492]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

6.92

Notes
[492] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.874 ^[493]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-6.31

upper limit

5.38

Notes
[493] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.78 ^[494]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-6.58

upper limit

4.95

Notes
[494] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.033 ^[495]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

6.85

Notes
[495] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.094 ^[496]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.81

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

6.1

Notes
[496] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.032 ^[497]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

7.49

Notes
[497] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[498]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

5.33

Confidence interval

level

95%

sides

2-sided

lower limit

1.77

upper limit

8.89

Notes
[498] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.808 ^[499]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-5.19

upper limit

6.64

Notes
[499] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.511 ^[500]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

-3.74

upper limit

7.48

Notes
[500] - MMRM analysis adjusted for FACIT Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Change from Baseline in Brief Fatigue Inventory (BFI) Question 3 at all assessment time points

Top of page

End point title

Change from Baseline in Brief Fatigue Inventory (BFI) Question 3 at all assessment time points

End point description

BFI is a self-reported instrument consisting of nine questions which correlate well with quality-of-life measures. For this study, Question 3 only was used which asked about fatigue severity at its worst in the last 24 hours. A discrete 11 unit numeric reporting scale was used where 0 =No fatigue, and 10=As bad as you can imagine. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 4, 12, 24

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[501]	37 ^[502]	37 ^[503]	37 ^[504]	37 ^[505]	37 ^[506]
Units: Scores on a scale
least squares mean (standard error)
Week 4,n=34,34,36,37, 36, 36\|	-0.60 ± 0.348	-0.67 ± 0.348	-1.10 ± 0.339	-1.60 ± 0.335	-1.86 ± 0.339	-1.53 ± 0.341
Week 12,n=34,35,35,37, 35, 36\|	-0.63 ± 0.346	-1.26 ± 0.342	-1.83 ± 0.341	-2.02 ± 0.333	-2.07 ± 0.341	-2.20 ± 0.339
Week 24,n=8,14,21,24, 19, 34\|	-1.83 ± 0.635	-2.19 ± 0.496	-1.76 ± 0.418	-2.03 ± 0.395	-2.59 ± 0.435	-2.41 ± 0.353

Notes
[501] - ITT Population.
[502] - ITT Population.
[503] - ITT Population.
[504] - ITT Population.
[505] - ITT Population.
[506] - ITT Population.

Stat 1

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.888 ^[507]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

0.9

Notes
[507] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 2

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.307 ^[508]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.46

upper limit

0.46

Notes
[508] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 3

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.041 ^[509]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-1.95

upper limit

-0.04

Notes
[509] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 4

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.191 ^[510]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.32

Notes
[510] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 5

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.014 ^[511]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.16

upper limit

-0.24

Notes
[511] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 6

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[512]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.39

Confidence interval

level

95%

sides

2-sided

lower limit

-2.34

upper limit

-0.45

Notes
[512] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 7

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 22.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.656 ^[513]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-1.94

upper limit

1.23

Notes
[513] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 8

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 45 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.928 ^[514]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

1.57

Notes
[514] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 9

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.788 ^[515]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.68

upper limit

1.28

Notes
[515] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 10

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.01 ^[516]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

-0.3

Notes
[516] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 11

Statistical analysis description

Week 4

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.059 ^[517]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-1.89

upper limit

0.03

Notes
[517] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 12

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.003 ^[518]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.44

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

-0.48

Notes
[518] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 13

Statistical analysis description

Week 12

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001 ^[519]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.57

Confidence interval

level

95%

sides

2-sided

lower limit

-2.53

upper limit

-0.62

Notes
[519] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 14

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 135 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.324 ^[520]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.28

upper limit

0.76

Notes
[520] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Stat 15

Statistical analysis description

Week 24

Comparison groups

Placebo v GSK3196165 180 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.432 ^[521]

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-2.02

upper limit

0.87

Notes
[521] - MMRM analysis adjusted for BFI Baseline score, treatment group, visit and treatment group by visit and Baseline by visit interactions.

Secondary: Number of participants with adverse events (AEs) and serious AEs (SAEs)

Top of page

End point title

Number of participants with adverse events (AEs) and serious AEs (SAEs)

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per Medical or Scientific judgment. Overall AEs and SAEs for the entire study duration until follow-up have been presented.

End point type

Secondary

End point timeframe

Up to 62 weeks

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[522]	37 ^[523]	37 ^[524]	37 ^[525]	37 ^[526]	37 ^[527]
Units: Participants
Any AE\|	26	24	26	28	28	24
Any SAE\|	1	2	1	2	2	0

Notes
[522] - ITT Population
[523] - ITT Population
[524] - ITT Population
[525] - ITT Population
[526] - ITT Population
[527] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with serious infections

Top of page

End point title

Number of participants with serious infections

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious infections were categorized as AE of special interest. The number of participants with overall serious infections have been presented.

End point type

Secondary

End point timeframe

Up to 62 weeks

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[528]	37 ^[529]	37 ^[530]	37 ^[531]	37 ^[532]	37 ^[533]
Units: Participants
number (not applicable)	0	1	0	0	0	0

Notes
[528] - ITT Population
[529] - ITT Population
[530] - ITT Population
[531] - ITT Population
[532] - ITT Population
[533] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with opportunistic infections

Top of page

End point title

Number of participants with opportunistic infections

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Opportunistic infections were categorized as AE of special interest. The number of participants with overall opportunistic infections have been presented.

End point type

Secondary

End point timeframe

Up to 62 weeks

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[534]	37 ^[535]	37 ^[536]	37 ^[537]	37 ^[538]	37 ^[539]
Units: Participants
number (not applicable)	0	0	0	0	0	0

Notes
[534] - ITT Population
[535] - ITT Population
[536] - ITT Population
[537] - ITT Population
[538] - ITT Population
[539] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with pulmonary events

Top of page

End point title

Number of participants with pulmonary events

End point description

Pulmonary assessments were performed to determine the number of participants with pulmonary events including persistent cough, persistent dyspnea, and persistent Diffusing capacity of the lung for carbon monoxide (DLCO). Persistent is defined as any event with duration >=15 days. Baseline was defined as the last available assessment prior to the start of study treatment. The number of participants experiencing pulmonary events have been reported.

End point type

Secondary

End point timeframe

Up to 62 weeks

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[540]	37 ^[541]	37 ^[542]	37 ^[543]	37 ^[544]	37 ^[545]
Units: Participants
Persistent Cough\|	1	0	0	0	0	0
Persistent Dyspnea\|	1	0	0	1	0	0
Persistent DLCO decrease >15% from Baseline\|	2	3	1	0	3	1

Notes
[540] - ITT Population
[541] - ITT Population
[542] - ITT Population
[543] - ITT Population
[544] - ITT Population
[545] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with worst-case Post-Baseline results for Pulse Oximetry

Top of page

End point title

Number of participants with worst-case Post-Baseline results for Pulse Oximetry

End point description

Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen, that is called as blood oxygen saturation. Baseline was defined as the last available assessment prior to the start of study treatment. The number of participants with blood oxygen level < 80%, 80% to <90% and >=90% have been reported. Only those participants with data available at specified time point were analyzed (represented by n=x in category titles).

End point type

Secondary

End point timeframe

Up to 62 weeks

End point values	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Number of subjects analysed	37 ^[546]	37 ^[547]	37 ^[548]	37 ^[549]	37 ^[550]	37 ^[551]
Units: Participants
< 80%; n=37, 36, 37, 37, 36, 37\|	0	0	0	0	0	0
80% to <90%; n=37, 36, 37, 37, 36, 37\|	0	0	0	0	1	0
>= 90%; n=37, 36, 37, 37, 36, 37\|	37	36	37	37	35	37

Notes
[546] - ITT Population
[547] - ITT Population
[548] - ITT Population
[549] - ITT Population
[550] - ITT Population
[551] - ITT Population

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 62 weeks

Adverse event reporting additional description

ITT Population was used for the analysis of safety data.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Placebo

Reporting group description

Participants received placebo liquid (sterile 0.9% weight/volume) sodium chloride solution) 0.6 mL drawn into a small (1 mL syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Reporting group title

GSK3196165 22.5 mg

Reporting group description

Participants received GSK3196165 22.5 mg (0.15 mL) liquid drawn into a small (03 ml/0.5 ml syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Reporting group title

GSK3196165 45 mg

Reporting group description

Participants received GSK3196165 45 mg (0.3 mL) liquid drawn into a small (03 ml/0.5 ml syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Reporting group title

GSK3196165 90 mg

Reporting group description

Participants received GSK3196165 90 mg (0.6 mL) liquid drawn into a small (1 ml syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Reporting group title

GSK3196165 135 mg

Reporting group description

Participants received GSK3196165 135 mg (0.9 mL) liquid drawn into a small (1 ml syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Reporting group title

GSK3196165 180 mg

Reporting group description

Participants received GSK3196165 180 mg (1.2 mL) liquid drawn into a small (2 ml/3 ml syringe) administered subcutaneous in the thigh/abdomen up to 52 weeks in combination with MTX tablets (orally)/liquid (subcutaneous injection) at a dose of 7.5 to 25 mg/week and folic acid tablet/capsule (orally) at a dose of >=5 mg/week. MTX was taken as a single weekly dose/divided weekly dose, folic acid was taken the day after and at least 12 hours following MTX administration. Safety was monitored for 1 hour after the injection, for the first 3 injections, then for 30 minutes thereafter.

Serious adverse events	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 37 (2.70%)	2 / 37 (5.41%)	1 / 37 (2.70%)	2 / 37 (5.41%)	2 / 37 (5.41%)	0 / 37 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	0 / 37 (0.00%)	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Oesophageal spasm
subjects affected / exposed	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pyelonephritis acute
subjects affected / exposed	0 / 37 (0.00%)	1 / 37 (2.70%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	GSK3196165 22.5 mg	GSK3196165 45 mg	GSK3196165 90 mg	GSK3196165 135 mg	GSK3196165 180 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	13 / 37 (35.14%)	12 / 37 (32.43%)	13 / 37 (35.14%)	9 / 37 (24.32%)	18 / 37 (48.65%)	13 / 37 (35.14%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 37 (5.41%)	1 / 37 (2.70%)	3 / 37 (8.11%)	3 / 37 (8.11%)	3 / 37 (8.11%)	0 / 37 (0.00%)
occurrences all number	2	1	8	3	4	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 37 (0.00%)	3 / 37 (8.11%)	1 / 37 (2.70%)	0 / 37 (0.00%)	3 / 37 (8.11%)	5 / 37 (13.51%)
occurrences all number	0	3	1	0	5	5
Infections and infestations
Nasopharyngitis
subjects affected / exposed	8 / 37 (21.62%)	5 / 37 (13.51%)	7 / 37 (18.92%)	5 / 37 (13.51%)	8 / 37 (21.62%)	9 / 37 (24.32%)
occurrences all number	8	6	11	6	8	12
Upper respiratory tract infection
subjects affected / exposed	3 / 37 (8.11%)	5 / 37 (13.51%)	3 / 37 (8.11%)	2 / 37 (5.41%)	7 / 37 (18.92%)	3 / 37 (8.11%)
occurrences all number	3	6	3	2	9	4

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Were there any global substantial amendments to the protocol? Yes

27 Feb 2015

This amendment includes removal of the Medical Monitor Contact Information on the Sponsor Information page, missing assessments in Section 7.1, and removal of example PRO Questionnaires as Appendix 12.7.

13 Mar 2015

This amendment includes revision of the study title on the Title page, clarification that actigraphy will only be at participating sites in Section 3, Section 7.2, Section 7.3, Section 7.10.5, Section 7.10.6, Appendix 12.7, minor revisions to placebo and comedications information in Section 6.1, changes to the guidance on dosing instructions in Section 6.1, and revisions of anchors for Global Assessment of Arthritis in Section 7.3.2.

01 May 2015

This amendment includes removal of flow cytometry assessments from Section 3, 7.1 and Section 7.7, clarification of biomarkers in Section 3, corrections to neutropenia levels in Section 4.7.1, clarification of Tuberculosis (TB) testing in Section 5.1 and Section 7.2, changes to administration of MTX in Section 6.1 and Section 6.9.2, clarification of unblinded administrator in Section 6.5, compliance of MTX in Section 6.8, and corrected Routine Laboratory Assessments in Section 7.4.11 (Table 2).

01 May 2015

This amendment includes removal of blank line in Section 7.1.

20 Oct 2015

This amendment includes additional criteria for continuation or withdrawal in the study at Week 38 in Section 4.2 and Section 5.4, clarification that SoC is standard of care in Section 4.5, clarification of rescreening procedure in Section 5.3.1, Section 5.3.2.2, clarification of DLCO retesting in Section 5.3.2, addition of lipid measurements in Section 7.1 and Section 7.4.11 (Table 2), clarification of header version numbers and footnotes in Section 7.1, clarification of eligibility in Section 7.3.5, clarification of pregnancy in Section 7.4.7, additions to Appendix 12.1, revisions of Appendix 12.2 and Appendix 12.5, and added Appendix 12.9 to track all protocol text changes.

25 Nov 2015

This amendment includes clarification that the DLCO tests may be repeated twice within the screening period in Section 5.1, clarification that only Fridericia’s formula (QTcF) will be used in Section 5.2 and Section 5.4.2, clarification that the screening ECG test may be repeated once in Section 5.3.2.3, clarification of footnotes in Section 7.1, removal of biomarker interleukin 22 (IL-22) measurement in Section 7.7, and reinsertion of contraception guidance inadvertently deleted in Appendix 12.2 of previous Amendment 5.

11 Mar 2016

This amendment includes correction of the example formula to calculate the EULAR good/moderate response at Week 12 and Week 36 in Section 4.2 and Section 6.4; confirmation of mandatory chest HRCT if DLCO ≥60% to <70% predicted in Section 5.1, Section 5.3.2.2, Section 7.1 and Section 7.4.1; update to investigator brochure (IB) document number and added reference in Section 11.

08 Jun 2016

Germany only: This local amendment revised Inclusion Criterion number13 to DLCO ≥70% predicted in Section 5.1.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination with Methotrexate Therapy, in Subjects with Active Moderate-Severe Rheumatoid Arthritis Despite Treatment with Methotrexate

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants who achieved disease activity score for 28 different joints with C-reactive protein value (DAS28{CRP}) remission (DAS28 <2.6) at Week 24

Primary: Percentage of participants who achieved disease activity score for 28 different joints with C-reactive protein value (DAS28{CRP}) remission (DAS28 <2.6) at Week 24

Secondary: Change from Baseline in DAS28(CRP) at Week 12

Secondary: Change from Baseline in DAS28(CRP) at Week 12

Secondary: Percentage of participants who achieved DAS28(CRP) remission (DAS28 <2.6) at all time points

Secondary: Percentage of participants who achieved DAS28(CRP) remission (DAS28 <2.6) at all time points

Secondary: Change from Baseline in DAS28(CRP) at all assessment time points

Secondary: Change from Baseline in DAS28(CRP) at all assessment time points

Secondary: Time to first DAS28(CRP) remission

Secondary: Time to first DAS28(CRP) remission

Secondary: Percentage of participants achieving categorical DAS28(CRP) response (moderate/good [European League against Rheumatism] EULAR response) at all assessment time points

Secondary: Percentage of participants achieving categorical DAS28(CRP) response (moderate/good [European League against Rheumatism] EULAR response) at all assessment time points

Secondary: Percentage of participants with American College of Rheumatology’s (ACR) 20/50/70 response rates at all assessment time points

Secondary: Percentage of participants with American College of Rheumatology’s (ACR) 20/50/70 response rates at all assessment time points

Secondary: Percentage of participants with Index-based ACR/EULAR remission rates at all assessment time points

Secondary: Percentage of participants with Index-based ACR/EULAR remission rates at all assessment time points

Secondary: Percentage of participants with Boolean-based ACR/EULAR remission rates at all assessment time points

Secondary: Percentage of participants with Boolean-based ACR/EULAR remission rates at all assessment time points

Secondary: Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission

Secondary: Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission

Secondary: Change from Baseline in SDAI at all assessment time points

Secondary: Change from Baseline in SDAI at all assessment time points

Secondary: Change from Baseline in CDAI at all assessment time points

Secondary: Change from Baseline in CDAI at all assessment time points

Secondary: Change from Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) at all assessment time points

Secondary: Change from Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) at all assessment time points

Secondary: Change from Baseline in pain score at all assessment time points

Secondary: Change from Baseline in pain score at all assessment time points

Secondary: Change from Baseline in physical and mental component scores (PCS, MCS) and in domain scores of short form 36 (SF-36) at all assessment time points

Secondary: Change from Baseline in physical and mental component scores (PCS, MCS) and in domain scores of short form 36 (SF-36) at all assessment time points

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at all assessment time points

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at all assessment time points

Secondary: Change from Baseline in Brief Fatigue Inventory (BFI) Question 3 at all assessment time points

Secondary: Change from Baseline in Brief Fatigue Inventory (BFI) Question 3 at all assessment time points

Secondary: Number of participants with adverse events (AEs) and serious AEs (SAEs)

Secondary: Number of participants with adverse events (AEs) and serious AEs (SAEs)

Secondary: Number of participants with serious infections

Secondary: Number of participants with serious infections

Secondary: Number of participants with opportunistic infections

Secondary: Number of participants with opportunistic infections

Secondary: Number of participants with pulmonary events

Secondary: Number of participants with pulmonary events

Secondary: Number of participants with worst-case Post-Baseline results for Pulse Oximetry

Secondary: Number of participants with worst-case Post-Baseline results for Pulse Oximetry

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination with Methotrexate Therapy, in Subjects with Active Moderate-Severe Rheumatoid Arthritis Despite Treatment with Methotrexate