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Clinical Trial Results:
A multi-centre Phase IIa double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in subjects with inflammatory hand osteoarthritis.

Summary
EudraCT number	2015-003089-96
Trial protocol	GB DE NL PL
Global end of trial date	29 Nov 2017

Results information
Results version number	v2(current)
This version publication date	12 Apr 2019
First version publication date	12 Dec 2018
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

204851

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, 1 866-435-7343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

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

13 Apr 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Nov 2017

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy potential of GSK3196165 on pain in inflammatory hand osteoarthritis.

Protection of trial subjects

Paracetamol (acetaminophen) was a permitted concomitant medication for hand pain, for the duration of this study and could be taken on an as needed basis up to 4gram per day or to the maximum permitted under local label.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Mar 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 11

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

Poland: 8

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

United States: 7

Worldwide total number of subjects

EEA total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a multi-center, double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in participants with inflammatory hand osteoarthritis. The study was conducted in five countries in Poland, United Kingdom, Netherlands, Germany and United States.

Screening details

A total 121 participants were screened of which 77 were screen failures and 44 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, Monitor, Carer, Data analyst, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).

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

Participants were administered sterile 0.9 percentage (w/v) sodium chloride solution.

GSK3196165 180mg

Arm description

Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).

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

Participants were administered 180 milligram (1.2 milliliter) of GSK3196165 aqueous solution of purified monoclonal antibody.

Number of subjects in period 1	Placebo	GSK3196165 180mg
Started	22	22
Completed	21	18
Not completed	1	4
Consent withdrawn by subject	1	1
Adverse event, non-fatal	-	2
Lost to follow-up	-	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

GSK3196165 180mg

Reporting group description

Reporting group values	Placebo	GSK3196165 180mg	Total
Number of subjects	22	22	44
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	19	17	36
From 65-84 years	3	5	8
85 years and over	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	56.7 ( 6.80 )	60.9 ( 6.25 )	-
Sex: Female, Male
Units: Subjects
Female	20	20	40
Male	2	2	4
Race/Ethnicity, Customized
Units: Subjects

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

GSK3196165 180mg

Reporting group description

Primary: Change from Baseline in 24-hour average hand pain intensity, averaged over the 7 days prior to Week 6

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End point title

Change from Baseline in 24-hour average hand pain intensity, averaged over the 7 days prior to Week 6

End point description

Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors “0” (no pain) and “10” (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo). n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Primary

End point timeframe

Baseline (Day 1 Pre-dose) and Week 6

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	21 ^[1]	20 ^[2]
Units: Scores on scale
least squares mean (standard error)	-1.34 ( 0.325 )	-1.70 ( 0.334 )

Notes
[1] - Intent To Treat Population.
[2] - Intent To Treat Population.

Difference from placebo for Week 6 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.442 ^[3]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

0.58

Notes
[3] - MMRM model with fixed effects of Baseline Value,Treatment Group,Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used.p-value corresponds to the difference over placebo measure and confidence interval

Secondary: Change from Baseline in 24 hours average hand pain intensity averaged over the 7 days prior to each visit

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End point title

Change from Baseline in 24 hours average hand pain intensity averaged over the 7 days prior to each visit

End point description

Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors “0” (no pain) and “10” (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score is calculated by sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Secondary

End point timeframe

Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[4]	22 ^[5]
Units: Scores on scale
least squares mean (standard error)
Week 1, n=22, 20	-0.13 ( 0.152 )	-0.59 ( 0.160 )
Week 2, n=21, 20	-0.48 ( 0.230 )	-0.86 ( 0.239 )
Week 3, n=21, 20	-0.74 ( 0.279 )	-1.24 ( 0.289 )
Week 4, n=21, 20	-0.91 ( 0.291 )	-1.65 ( 0.301 )
Week 6, n=21, 20	-1.34 ( 0.325 )	-1.70 ( 0.334 )
Week 8, n=20, 19	-1.27 ( 0.382 )	-2.10 ( 0.393 )
Week 10, n=20, 19	-1.18 ( 0.376 )	-2.09 ( 0.389 )
Week 12, n=19, 18	-1.35 ( 0.402 )	-2.24 ( 0.416 )

Notes
[4] - Intent-to-Treat Population.
[5] - Intent-to-Treat Population.

Difference from placebo for Week 1 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.046 ^[6]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.01

Notes
[6] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 2 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.257 ^[7]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

0.29

Notes
[7] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 3 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.22 ^[8]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

0.31

Notes
[8] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 4 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.085 ^[9]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.59

upper limit

0.11

Notes
[9] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 6 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.442 ^[10]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

0.58

Notes
[10] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 8 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.139 ^[11]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

0.28

Notes
[11] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 10 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.103 ^[12]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.19

Notes
[12] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 12 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.132 ^[13]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-2.06

upper limit

0.28

Notes
[13] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Change from Baseline of worst hand pain intensity over 24 hours averaged over the 7 days prior to each visit

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End point title

Change from Baseline of worst hand pain intensity over 24 hours averaged over the 7 days prior to each visit

End point description

Participants were required to complete a daily pain NRS based on their 24-hour worst hand pain intensity with the anchors “0” (no pain) and “10” (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The score is calculated as sum of daily 24 hours worst hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Secondary

End point timeframe

Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[14]	22 ^[15]
Units: Scores on scale
least squares mean (standard error)
Week 1, n=22, 20	0.01 ( 0.174 )	-0.45 ( 0.183 )
Week 2, n=21, 20	-0.42 ( 0.235 )	-0.69 ( 0.245 )
Week 3, n=21, 20	-0.63 ( 0.269 )	-1.23 ( 0.278 )
Week 4, n= 21, 20	-0.72 ( 0.289 )	-1.51 ( 0.299 )
Week 6, n= 21, 20	-1.30 ( 0.328 )	-1.63 ( 0.337 )
Week 8, n= 20, 19	-1.18 ( 0.394 )	-2.11 ( 0.406 )
Week 10, n= 20, 19	-1.15 ( 0.394 )	-2.13 ( 0.407 )
Week 12, n= 19, 18	-1.32 ( 0.415 )	-2.34 ( 0.430 )

Notes
[14] - Intent-to-Treat Population.
[15] - Intent-to-Treat Population.

Difference from placebo for Week 1 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.082 ^[16]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

0.06

Notes
[16] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 2 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.426 ^[17]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

0.41

Notes
[17] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 3 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.129 ^[18]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.38

upper limit

0.18

Notes
[18] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 4 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.067 ^[19]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

0.06

Notes
[19] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 6 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.494 ^[20]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

0.63

Notes
[20] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 8 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.107 ^[21]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

0.21

Notes
[21] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 10 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.092 ^[22]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.13

upper limit

0.17

Notes
[22] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 12 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.098 ^[23]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

0.2

Notes
[23] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

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End point title

Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

End point description

Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 30 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is reported. Participants with missing data at a particular visit had been assumed to be non-responders.

End point type

Secondary

End point timeframe

Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[24]	22 ^[25]
Units: Percentage of participants
Week 1	0	9
Week 2	0	18
Week 3	5	23
Week 4	14	41
Week 6	23	45
Week 8	18	50
Week 10	18	50
Week 12	23	45
Follow up (Week 22)	23	27

Notes
[24] - Intent-to-Treat Population.
[25] - Intent-to-Treat Population.

No statistical analyses for this end point

Secondary: Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

Top of page

End point title

Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

End point description

Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 50 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented. Participants with missing data at a particular visit had been assumed to be non-responders.

End point type

Secondary

End point timeframe

Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[26]	22 ^[27]
Units: Percentage of participants
Week 1	0	0
Week 2	0	9
Week 3	0	18
Week 4	0	23
Week 6	14	27
Week 8	14	41
Week 10	9	36
Week 12	14	41
Follow up (Week 22)	9	23

Notes
[26] - Intent-to-Treat Population.
[27] - Intent-to-Treat Population.

No statistical analyses for this end point

Secondary: Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

Top of page

End point title

Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

End point description

Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 30 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented. Participants with missing data at a particular visit had been assumed to be non-responders.

End point type

Secondary

End point timeframe

Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[28]	22 ^[29]
Units: Percentage of participants
Week 1	0	9
Week 2	0	18
Week 3	0	23
Week 4	0	32
Week 6	9	36
Week 8	9	45
Week 10	14	45
Week 12	14	45
Follow up (Week 22)	14	32

Notes
[28] - Intent-to-Treat Population.
[29] - Intent-to-Treat Population.

No statistical analyses for this end point

Secondary: Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

Top of page

End point title

Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

End point description

Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 50 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented. Participants with missing data at a particular visit had been assumed to be non-responders.

End point type

Secondary

End point timeframe

Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[30]	22 ^[31]
Units: Percentage of participants
Week 1	0	0
Week 2	0	5
Week 3	0	14
Week 4	0	18
Week 6	5	18
Week 8	5	32
Week 10	5	27
Week 12	9	36
Follow up (Week 22)	5	23

Notes
[30] - Intent-to-Treat Population.
[31] - Intent-to-Treat Population.

No statistical analyses for this end point

Secondary: Change from Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS scores at each visit.

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End point title

Change from Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS scores at each visit.

End point description

The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours. All items are rated on NRS scale with anchors “0” (none) to “10” (extreme). The scores for the pain and physical function components were calculated as simple summation of the item scores relating to that domain, so the Pain component ranges from 0 (i.e. all pain item scores are scored 0 [none]) to 50 (i.e. all pain item scores are scored 10 [extreme]), and the Physical Function component ranges from 0 (i.e. all physical function item scores are scored 0 [none]) to 90 (i.e. all physical function item scores are scored 10 [extreme]). The total AUSCAN score was calculated as simple summation of the 15 item scores and therefore ranges from 0 to 150. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

End point type

Secondary

End point timeframe

Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[32]	22 ^[33]
Units: Scores on scale
least squares mean (standard error)
Pain, Week 1, n=22, 20	0.8 ( 0.98 )	-1.9 ( 1.03 )
Pain, Week 2, n=21, 21	-1.8 ( 1.27 )	-3.7 ( 1.28 )
Pain, Week 4, n=22, 21	-3.5 ( 1.61 )	-7.2 ( 1.64 )
Pain, Week 6, n=22, 21	-6.6 ( 1.72 )	-7.6 ( 1.76 )
Pain, Week 8, n=20, 20	-4.9 ( 1.93 )	-8.7 ( 1.97 )
Pain, Week 10, n=20, 20	-5.3 ( 1.82 )	-10.9 ( 1.87 )
Pain, Week 12, n=21,19	-4.6 ( 1.84 )	-9.3 ( 1.91 )
Stiffness, Week 1, n= 22, 20	-0.4 ( 0.29 )	-0.6 ( 0.31 )
Stiffness, Week 2, n= 21, 21	-0.8 ( 0.33 )	-1.1 ( 0.33 )
Stiffness, Week 4, n= 22, 21	-1.2 ( 0.41 )	-1.8 ( 0.42 )
Stiffness, Week 6, n= 22, 21	-1.4 ( 0.39 )	-1.6 ( 0.40 )
Stiffness, Week 8, n= 20, 20	-1.2 ( 0.41 )	-1.9 ( 0.42 )
Stiffness, Week 10, n= 20, 20	-1.6 ( 0.44 )	-2.2 ( 0.45 )
Stiffness, Week 12, n= 21, 19	-1.5 ( 0.45 )	-2.2 ( 0.47 )
Physical function, Week 1, n=22, 20	-0.7 ( 2.08 )	-3.6 ( 2.16 )
Physical function, Week 2, n=21,21	-2.8 ( 2.35 )	-5.7 ( 2.37 )
Physical function, Week 4, n=22, 21	-6.4 ( 3.01 )	-11.3 ( 3.07 )
Physical function, Week 6, n=22, 21	-9.1 ( 3.25 )	-11.8 ( 3.32 )
Physical function, Week 8, n=20, 20	-8.3 ( 3.57 )	-13.2 ( 3.64 )
Physical function, Week 10, n=20, 20	-9.0 ( 3.82 )	-15.2 ( 3.92 )
Physical function, Week 12, n=21, 19	-7.2 ( 3.74 )	-15.4 ( 3.87 )
Total, Week 1, n= 22, 20	-0.5 ( 3.07 )	-6.0 ( 3.20 )
Total, Week 2, n= 21, 21	-5.7 ( 3.66 )	-10.4 ( 3.70 )
Total, Week 4, n= 22, 21	-11.4 ( 4.72 )	-20.1 ( 4.83 )
Total, Week 6, n= 22, 21	-17.3 ( 5.17 )	-20.7 ( 5.28 )
Total, Week 8, n= 20, 20	-14.6 ( 5.70 )	-23.6 ( 5.81 )
Total, Week 10, n= 20, 20	-16.1 ( 5.88 )	-28.2 ( 6.04 )
Total, Week 12, n= 21, 19	-13.5 ( 5.92 )	-26.7 ( 6.12 )

Notes
[32] - Intent-to-Treat Population.
[33] - Intent-to-Treat Population.

For Pain component, Week 1

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.061 ^[34]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

0.1

Notes
[34] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Pain component, Week 2

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.282 ^[35]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

1.7

Notes
[35] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Pain componentWeek 4

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.113 ^[36]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

0.9

Notes
[36] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Pain component, Week 6

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.695 ^[37]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

Notes
[37] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Pain component, Week 8

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.176 ^[38]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

1.8

Notes
[38] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Pain component, Week 10

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.041 ^[39]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.8

upper limit

-0.2

Notes
[39] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Pain component, Week 12

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.082 ^[40]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

0.6

Notes
[40] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Stiffness component, Week 1

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.587 ^[41]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.6

Notes
[41] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Stiffness component, Week 2

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.457 ^[42]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.6

Notes
[42] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Stiffness component, Week 4

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.298 ^[43]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.6

Notes
[43] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Stiffness component, Week 6

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.726 ^[44]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.9

Notes
[44] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Stiffness component, Week 8

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.213 ^[45]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.4

Notes
[45] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Stiffness component, Week 10

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.331 ^[46]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.7

Notes
[46] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Stiffness component, Week 12

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.248 ^[47]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.6

Notes
[47] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Physical Function component, Week 1

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.35 ^[48]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

3.3

Notes
[48] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Physical Function component, Week 2

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.383 ^[49]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-9.8

upper limit

3.8

Notes
[49] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Physical Function component, Week 4

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.271 ^[50]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-13.5

upper limit

3.9

Notes
[50] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Physical Function component, Week 6

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.565 ^[51]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-12.1

upper limit

6.7

Notes
[51] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval

For Physical Function component, Week 8

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.343 ^[52]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-15.2

upper limit

5.4

Notes
[52] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Physical Function component, Week 10

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.266 ^[53]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-17.3

upper limit

4.9

Notes
[53] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Physical Function component, Week 12

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.136 ^[54]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-8.2

Confidence interval

level

95%

sides

2-sided

lower limit

-19.1

upper limit

2.7

Notes
[54] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 1

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.23 ^[55]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-14.5

upper limit

3.6

Notes
[55] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 2

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.381 ^[56]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-15.2

upper limit

5.9

Notes
[56] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 4

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.207 ^[57]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-22.4

upper limit

Notes
[57] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 6

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.648 ^[58]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-18.4

upper limit

11.6

Notes
[58] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 8

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.278 ^[59]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-9

Confidence interval

level

95%

sides

2-sided

lower limit

-25.4

upper limit

7.5

Notes
[59] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 10

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.16 ^[60]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-12.1

Confidence interval

level

95%

sides

2-sided

lower limit

-29.1

upper limit

Notes
[60] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

For Total of all component scores, Week 12

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.127 ^[61]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-13.3

Confidence interval

level

95%

sides

2-sided

lower limit

-30.5

upper limit

3.9

Notes
[61] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Change from Baseline in number of soft tissue swollen hand joints at each visit

Top of page

End point title

Change from Baseline in number of soft tissue swollen hand joints at each visit

End point description

Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Secondary

End point timeframe

Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[62]	22 ^[63]
Units: Swollen joints
least squares mean (standard error)
Week 1, n = 22, 21\|	-0.3 ( 0.64 )	-0.3 ( 0.66 )
Week 2, n = 21, 21\|	-1.6 ( 0.85 )	-1.2 ( 0.86 )
Week 4, n = 22, 21\|	-1.6 ( 0.76 )	-2.1 ( 0.78 )
Week 6, n = 22, 21\|	-3.7 ( 0.83 )	-2.3 ( 0.85 )
Week 8, n = 20, 20\|	-3.0 ( 0.92 )	-2.8 ( 0.94 )
Week 10, n = 20, 20\|	-2.6 ( 1.08 )	-2.9 ( 1.10 )
Week 12, n = 21, 19\|	-2.9 ( 0.91 )	-3.1 ( 0.93 )

Notes
[62] - Intent-to-Treat Population.
[63] - Intent-to-Treat Population.

Difference from placebo for Week 1 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.957 ^[64]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.8

Notes
[64] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 2 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.775 ^[65]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.8

Notes
[65] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 4 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.624 ^[66]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

1.7

Notes
[66] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 6 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.243 ^[67]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

3.8

Notes
[67] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 8 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.875 ^[68]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

2.9

Notes
[68] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 10 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.848 ^[69]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

2.8

Notes
[69] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 12 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.883 ^[70]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

2.4

Notes
[70] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Change from Baseline in number of tender hand joints at each visit

Top of page

End point title

Change from Baseline in number of tender hand joints at each visit

End point description

Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored >0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Secondary

End point timeframe

Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[71]	22 ^[72]
Units: Scores on scale
least squares mean (standard error)
Week 1, n= 22, 21	-0.6 ( 1.10 )	-1.8 ( 1.13 )
Week 2, n= 21, 21	-1.7 ( 1.15 )	-2.1 ( 1.17 )
Week 4, n= 22, 21	-1.1 ( 1.33 )	-3.0 ( 1.36 )
Week 6, n= 22, 21	-3.7 ( 1.27 )	-4.2 ( 1.30 )
Week 8, n= 20, 20	-2.4 ( 1.36 )	-3.9 ( 1.39 )
Week 10, n= 20, 20	-3.7 ( 1.45 )	-4.4 ( 1.48 )
Week 12, n= 21, 19	-3.5 ( 1.46 )	-4.0 ( 1.51 )

Notes
[71] - Intent-to-Treat Population.
[72] - Intent-to-Treat Population.

Difference from placebo for Week 1 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.463 ^[73]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

Notes
[73] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 2 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.809 ^[74]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

2.9

Notes
[74] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 4 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.324 ^[75]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

Notes
[75] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 6 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.783 ^[76]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

3.2

Notes
[76] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 8 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.464 ^[77]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

2.5

Notes
[77] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 10 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.736 ^[78]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

3.5

Notes
[78] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 12 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.806 ^[79]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

3.7

Notes
[79] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Change from Baseline in physician global assessment (PhGA) of disease activity

Top of page

End point title

Change from Baseline in physician global assessment (PhGA) of disease activity

End point description

Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Secondary

End point timeframe

Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[80]	22 ^[81]
Units: Scores on scale
least squares mean (standard error)
Week 2, n= 19, 14	-1.8 ( 0.39 )	-1.5 ( 0.45 )
Week 4, n= 20, 15	-2.1 ( 0.44 )	-2.6 ( 0.50 )
Week 8, n= 17, 15	-2.2 ( 0.52 )	-3.4 ( 0.57 )
Week 12, n= 18, 14	-2.7 ( 0.56 )	-3.0 ( 0.63 )

Notes
[80] - Intent-to-Treat Population.
[81] - Intent-to-Treat Population.

Difference from placebo for Week 2 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.586 ^[82]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.6

Notes
[82] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 4 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.416 ^[83]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.8

Notes
[83] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 8 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.12 ^[84]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

0.3

Notes
[84] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 12 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.687 ^[85]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

1.4

Notes
[85] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Change from Baseline in patient global assessment (PtGA) of disease activity

Top of page

End point title

Change from Baseline in patient global assessment (PtGA) of disease activity

End point description

Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, and 12

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22 ^[86]	22 ^[87]
Units: Scores on scale
least squares mean (standard error)
Week 2, n= 20, 21	-0.4 ( 0.36 )	-0.6 ( 0.35 )
Week 4, n= 21, 21	-0.6 ( 0.42 )	-1.3 ( 0.42 )
Week 8, n= 19, 20	-0.9 ( 0.47 )	-1.8 ( 0.46 )
Week 12, n= 20, 19	-0.7 ( 0.46 )	-1.8 ( 0.46 )

Notes
[86] - Intent-to-Treat Population.
[87] - Intent-to-Treat Population.

Difference from placebo for Week 2 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.651 ^[88]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.8

Notes
[88] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 4 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.271 ^[89]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.5

Notes
[89] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 8 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.186 ^[90]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

0.4

Notes
[90] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Difference from placebo for Week 12 is presented

Comparison groups

Placebo v GSK3196165 180mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.109 ^[91]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference (net)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

0.2

Notes
[91] - MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.

Secondary: Number of participants with adverse events (AE) and serious adverse events (SAE)

Top of page

End point title

Number of participants with adverse events (AE) and serious adverse events (SAE)

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who received at least one dose of study treatment (GSK3196165 or placebo) were included in Safety Population.

End point type

Secondary

End point timeframe

Up to Week 22

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22	22
Units: Participants
Any AE	11	13
Any SAE	1	2

No statistical analyses for this end point

Secondary: Number of participants with infections

Top of page

End point title

Number of participants with infections

End point description

Adverse events of special interest (AESI) included serious infections like serious respiratory infections and tuberculosis and other opportunistic infections. Number of participants with infections has been reported.

End point type

Secondary

End point timeframe

Up to Week 22

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22	22
Units: Participants
Serious Infections	0	0
Opportunistic Infections	0	0

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 events like pulmonary alveolar proteinosis (PAP), persistent (for 3 consecutive weeks) reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) > 15 percentage, persistent (for 3 consecutive weeks) cough and/or dyspnea and non- life threatening pulmonary changes related to surfactant accumulation is presented.

End point type

Secondary

End point timeframe

Up to Week 22

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22	22
Units: Participants
Persistent dyspnea	0	0
Persistent decrease in DLCO	0	0
Persistent Cough	0	0
Abnormal Lung Auscultation	0	0
PAP	0	0

No statistical analyses for this end point

Secondary: Number of participants with anti-GSK3196165 binding antibodies

Top of page

End point title

Number of participants with anti-GSK3196165 binding antibodies

End point description

Serum samples were collected at indicated time points for anti-drug antibody (ADA) measurements. Anti-GSK3196165 binding antibody detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. The number of participants with change from Baseline to any time post Baseline in the results of immunogenicity assessment as indicated by: negative to positive, positive to positive, positive to negative and negative to negative are presented.

End point type

Secondary

End point timeframe

Up to Week 22

End point values	Placebo	GSK3196165 180mg
Number of subjects analysed	22	22
Units: Participants
Negative to positive	0	1
Positive to positive	0	0
Positive to negative	0	0
Negative to negative	22	20

No statistical analyses for this end point

Secondary: Apparent clearance after subcutaneous administration (CL/F) of GSK3196165

Top of page

End point title

Apparent clearance after subcutaneous administration (CL/F) of GSK3196165 ^[92]

End point description

Blood samples were collected at indicated time points and CL/F was estimated using population PK analysis. Participants in the ‘Safety’ population who have at least one valid PK assessment were included Pharmacokinetic (PK) Population.

End point type

Secondary

End point timeframe

Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	GSK3196165 180mg
Number of subjects analysed	21 ^[93]
Units: Liters per day
geometric mean (geometric coefficient of variation)	4.94 ( 68.8 )

Notes
[93] - PK Population

No statistical analyses for this end point

Secondary: Apparent steady state volume of distribution after subcutaneous administration (Vss/F) of GSK3196165

Top of page

End point title

Apparent steady state volume of distribution after subcutaneous administration (Vss/F) of GSK3196165 ^[94]

End point description

Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis.

End point type

Secondary

End point timeframe

Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Notes
[94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	GSK3196165 180mg
Number of subjects analysed	21 ^[95]
Units: Liters
geometric mean (geometric coefficient of variation)	36.5 ( 61.5 )

Notes
[95] - PK Population

No statistical analyses for this end point

Secondary: Absoption rate constant (Ka) of GSK3196165

Top of page

End point title

Absoption rate constant (Ka) of GSK3196165 ^[96]

End point description

Blood samples were collected at indicated time points and Ka was estimated using population PK analysis.

End point type

Secondary

End point timeframe

Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Notes
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	GSK3196165 180mg
Number of subjects analysed	21 ^[97]
Units: Per day
geometric mean (geometric coefficient of variation)	0.205 ( 72.3 )

Notes
[97] - PK Population

No statistical analyses for this end point

Secondary: Serum concentration of GSK3196165 by visit

Top of page

End point title

Serum concentration of GSK3196165 by visit ^[98]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)

Notes
[98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	GSK3196165 180mg
Number of subjects analysed	22 ^[99]
Units: Nanogram per milliliter
geometric mean (geometric coefficient of variation)
Day 3, n = 18	2457.05 ( 94.74 )
Week 1, n = 21	1767.55 ( 46.96 )
Week 4, n = 21	2821.12 ( 61.00 )
Week 6, n = 20	1802.09 ( 60.42 )
Week 12, n = 8	800.96 ( 176.33 )
Follow up (Week 22), n = 12	56.40 ( 346.41 )

Notes
[99] - PK Population

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.

Adverse event reporting additional description

Non-serious AEs and SAE for Safety Population was reported.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Placebo

Reporting group description

Reporting group title

GSK3196165 180mg

Reporting group description

Serious adverse events	Placebo	GSK3196165 180mg
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 22 (4.55%)	2 / 22 (9.09%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
HUMERUS FRACTURE
subjects affected / exposed	0 / 22 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
HYPERTENSIVE CRISIS
subjects affected / exposed	0 / 22 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	1 / 22 (4.55%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	GSK3196165 180mg
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 22 (18.18%)	10 / 22 (45.45%)
Cardiac disorders
PALPITATIONS
subjects affected / exposed	2 / 22 (9.09%)	0 / 22 (0.00%)
occurrences all number	2	0
General disorders and administration site conditions
INJECTION SITE ERYTHEMA
subjects affected / exposed	0 / 22 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	3
INJECTION SITE RASH
subjects affected / exposed	0 / 22 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	6
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	2 / 22 (9.09%)	2 / 22 (9.09%)
occurrences all number	3	2
Infections and infestations
CONJUNCTIVITIS
subjects affected / exposed	0 / 22 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	2
HERPES ZOSTER
subjects affected / exposed	0 / 22 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	2
NASOPHARYNGITIS
subjects affected / exposed	1 / 22 (4.55%)	2 / 22 (9.09%)
occurrences all number	1	3
URINARY TRACT INFECTION
subjects affected / exposed	0 / 22 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	2

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

16 Nov 2015

Amendment No. 1: Correction of contraceptive requirements in Appendix 5, in response to regulatory review comments. Minor correction of question number in post-treatment interview guidance.

03 Jan 2017

Amendment No. 2: Amendment of inclusion criteria, #2, #3 and #5, clarification of exclusion criteria #9 and amendment of exclusion criteria #19(d). Addition of two planned interim analyses to Section Data Analysis Considerations and associated update to study blinding details. Addition of two PK sample time points (one on Day 85 and one on Day 155). Further minor corrections and clarifications to wording throughout the protocol.

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 multi-centre Phase IIa double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in subjects with inflammatory hand osteoarthritis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in 24-hour average hand pain intensity, averaged over the 7 days prior to Week 6

Primary: Change from Baseline in 24-hour average hand pain intensity, averaged over the 7 days prior to Week 6

Secondary: Change from Baseline in 24 hours average hand pain intensity averaged over the 7 days prior to each visit

Secondary: Change from Baseline in 24 hours average hand pain intensity averaged over the 7 days prior to each visit

Secondary: Change from Baseline of worst hand pain intensity over 24 hours averaged over the 7 days prior to each visit

Secondary: Change from Baseline of worst hand pain intensity over 24 hours averaged over the 7 days prior to each visit

Secondary: Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

Secondary: Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

Secondary: Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

Secondary: Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours average hand pain intensity at each visit

Secondary: Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

Secondary: Percentage of participants achieving a 30 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

Secondary: Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

Secondary: Percentage of participants achieving a 50 percentage reduction from Baseline in 24 hours worst hand pain intensity at each visit

Secondary: Change from Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS scores at each visit.

Secondary: Change from Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS scores at each visit.

Secondary: Change from Baseline in number of soft tissue swollen hand joints at each visit

Secondary: Change from Baseline in number of soft tissue swollen hand joints at each visit

Secondary: Change from Baseline in number of tender hand joints at each visit

Secondary: Change from Baseline in number of tender hand joints at each visit

Secondary: Change from Baseline in physician global assessment (PhGA) of disease activity

Secondary: Change from Baseline in physician global assessment (PhGA) of disease activity

Secondary: Change from Baseline in patient global assessment (PtGA) of disease activity

Secondary: Change from Baseline in patient global assessment (PtGA) of disease activity

Secondary: Number of participants with adverse events (AE) and serious adverse events (SAE)

Secondary: Number of participants with adverse events (AE) and serious adverse events (SAE)

Secondary: Number of participants with infections

Secondary: Number of participants with infections

Secondary: Number of participants with pulmonary events

Secondary: Number of participants with pulmonary events

Secondary: Number of participants with anti-GSK3196165 binding antibodies

Secondary: Number of participants with anti-GSK3196165 binding antibodies

Secondary: Apparent clearance after subcutaneous administration (CL/F) of GSK3196165

Secondary: Apparent clearance after subcutaneous administration (CL/F) of GSK3196165

Secondary: Apparent steady state volume of distribution after subcutaneous administration (Vss/F) of GSK3196165

Secondary: Apparent steady state volume of distribution after subcutaneous administration (Vss/F) of GSK3196165

Secondary: Absoption rate constant (Ka) of GSK3196165

Secondary: Absoption rate constant (Ka) of GSK3196165

Secondary: Serum concentration of GSK3196165 by visit

Secondary: Serum concentration of GSK3196165 by visit

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A multi-centre Phase IIa double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in subjects with inflammatory hand osteoarthritis.