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Clinical Trial Results:
A multicentre randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety, tolerability, efficacy, dose-response, pharmacokinetics and pharmacodynamics of repeat dosing of an anti-LAG3 cell depleting monoclonal antibody (GSK2831781) in patients with active ulcerative colitis

Summary
EudraCT number	2018-003278-28
Trial protocol	GB HU CZ FR BG PL NL BE
Global end of trial date	17 May 2021

Results information
Results version number	v1
This version publication date	01 Mar 2022
First version publication date	01 Mar 2022
Other versions	v2

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

204869

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, TW8 9GS

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

04 Aug 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 May 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

- To evaluate the safety and tolerability of repeat doses of GSK2831781 during the Double-Blind Induction Phase. - To characterise the efficacy dose response of GSK2831781 during the Double-Blind Induction Phase

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

06 May 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 1

Country: Number of subjects enrolled

Czechia: 4

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

India: 3

Country: Number of subjects enrolled

Japan: 1

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

Poland: 46

Country: Number of subjects enrolled

Russian Federation: 8

Country: Number of subjects enrolled

Slovakia: 2

Country: Number of subjects enrolled

South Africa: 5

Country: Number of subjects enrolled

Ukraine: 17

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

United States: 7

Worldwide total number of subjects

104

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)

100

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a randomized, placebo-controlled study to evaluate the safety, tolerability, efficacy and dose-response of GSK2831781 in participants with ulcerative colitis. The study was conducted across 13 countries.

Screening details

A total of 104 participants were enrolled in the study. This study was terminated based on the assessment of clinical data.

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 IV

Arm description

Participants were administered placebo via the intravenous (IV) route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy. Participants from the placebo arm identified as responders based on Week 10 assessments during the Induction Phase received placebo subcutaneously (SC) every 4 weeks from Weeks 14 to 26 during the 20 week double-blind extended treatment phase (ETP). At Week 30, participants underwent an assessment following which they were followed up until Week 42.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate and solvent for concentrate for solution for infusion, Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo was 0.9% weight/volume (w/v) sodium chloride solution to be administered via the IV route

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

Placebo was 0.9% w/v sodium chloride solution to be administered via the SC route

GSK2831781 450 mg IV

Arm description

Participants were administered GSK2831781 450 milligrams (mg) via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy. Participants identified as responders based on Week 10 assessments during the Induction Phase received GSK2831781 300 mg SC every 4 weeks from Weeks 14 to 26 during the 20-week double-blind ETP. At Week 30, participants underwent an assessment following which they were followed up until Week 42. Participants identified as non-responders during the double-blind Induction phase at Week 10 were administered GSK2831781 450 mg IV on Weeks 12, 14, 18 and 22 during the open-label (OL) induction phase. Participants from the Open-label induction phase who responded at Week 22 entered the 20-week (Week 22 to Week 42) open-label extended treatment phase and received GSK2831781 300 mg SC every 4 weeks from Week 26 until Week 38. Participants were followed up until Week 54.

Arm type

Experimental

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 milligrams per milliliter (mg/mL) to be administered via the IV route

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 mg/mL to be administered via the SC route

GSK2831781 300 mg IV

Arm description

Participants were administered GSK2831781 300 mg via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy. Participants identified as responders based on Week 10 assessments during the Induction Phase received GSK2831781 300 mg SC every 4 weeks from Weeks 14 to 26 during the 20-week double-blind ETP. At Week 30, participants underwent an assessment following which they were followed up until Week 42. Participants identified as non-responders during the double-blind Induction phase at Week 10 were administered GSK2831781 450 mg IV on Weeks 12, 14, 18 and 22 during the open-label (OL) induction phase. Participants from the Open-label induction phase who responded at Week 22 entered the 20-week (Week 22 to Week 42) open-label extended treatment phase and received GSK2831781 300 mg SC every 4 weeks from Week 26 until Week 38. Participants were followed up until Week 54.

Arm type

Experimental

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 mg/mL to be administered via the SC route

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 milligrams per milliliter (mg/mL) to be administered via the IV route

GSK2831781 150 mg IV

Arm description

Participants were administered GSK2831781 150 mg via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy. Participants identified as responders based on Week 10 assessments during the Induction Phase received GSK2831781 300 mg SC every 4 weeks from Weeks 14 to 26 during the 20-week double-blind ETP. At Week 30, participants underwent an assessment following which they were followed up until Week 42. Participants identified as non-responders during the double-blind Induction phase at Week 10 were administered GSK2831781 450 mg IV on Weeks 12, 14, 18 and 22 during the open-label (OL) induction phase. Participants from the Open-label induction phase who responded at Week 22 entered the 20-week (Week 22 to Week 42) open-label extended treatment phase and received GSK2831781 300 mg SC every 4 weeks from Week 26 until Week 38. Participants were followed up until Week 54.

Arm type

Experimental

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 mg/mL to be administered via the SC route

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 milligrams per milliliter (mg/mL) to be administered via the IV route

GSK2831781 45 mg IV

Arm description

Participants were administered GSK2831781 45 mg via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy. Participants identified as responders based on Week 10 assessments during the Induction Phase received GSK2831781 300 mg SC every 4 weeks from Weeks 14 to 26 during the 20-week double-blind ETP. At Week 30, participants underwent an assessment following which they were followed up until Week 42. Participants identified as non-responders during the double-blind Induction phase at Week 10 were administered GSK2831781 450 mg IV on Weeks 12, 14, 18 and 22 during the open-label (OL) induction phase. Participants from the Open-label induction phase who responded at Week 22 entered the 20-week (Week 22 to Week 42) open-label extended treatment phase and received GSK2831781 300 mg SC every 4 weeks from Week 26 until Week 38. Participants were followed up until Week 54.

Arm type

Experimental

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 mg/mL to be administered via the SC route

Investigational medicinal product name

GSK2831781

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

GSK2831781 was available as solution at unit dose strength of 150 milligrams per milliliter (mg/mL) to be administered via the IV route

Number of subjects in period 1	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Started	27	48	11	10	8
Completed	3	9	0	0	0
Not completed	24	39	11	10	8
Consent withdrawn by subject	4	6	-	1	-
Physician decision	-	1	-	-	-
Protocol-specified withdrawal criterion met	-	2	-	-	-
Adverse event, non-fatal	-	3	1	1	-
Study terminated by sponsor	17	18	10	7	8
Lost to follow-up	-	1	-	-	-
Lack of efficacy	3	8	-	1	-

Baseline characteristics

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Reporting group title

Placebo IV

Reporting group description

Reporting group title

GSK2831781 450 mg IV

Reporting group description

Reporting group title

GSK2831781 300 mg IV

Reporting group description

Reporting group title

GSK2831781 150 mg IV

Reporting group description

Reporting group title

GSK2831781 45 mg IV

Reporting group description

Reporting group values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV	Total
Number of subjects	27	48	11	10	8	104
Age categorical
Units: Participants
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age <37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	25	47	11	9	8	100
From 65-84 years	2	1	0	1	0	4
85 years and over	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	43.9 ( 12.82 )	40.7 ( 12.70 )	37.6 ( 13.06 )	42.5 ( 15.06 )	40.6 ( 10.60 )	-
Sex: Female, Male
Units: Participants
Female	12	22	4	4	1	43
Male	15	26	7	6	7	61
Race/Ethnicity, Customized
Units: Subjects
Asian-Central/South Asian Heritage	0	1	1	0	1	3
Asian-East Asian Heritage	2	0	0	0	0	2
Asian-Japanese Heritage	0	0	1	0	0	1
Asian-South East Asian Heritage	0	1	0	0	0	1
White-Arabic/North African Heritage	0	1	0	0	0	1
White-White/Caucasian/European Heritage	25	44	9	10	7	95
Mixed White race	0	1	0	0	0	1

End points

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Reporting group title

Placebo IV

Reporting group description

Reporting group title

GSK2831781 450 mg IV

Reporting group description

Reporting group title

GSK2831781 300 mg IV

Reporting group description

Reporting group title

GSK2831781 150 mg IV

Reporting group description

Reporting group title

GSK2831781 45 mg IV

Reporting group description

Subject analysis set title

Placebo SC

Subject analysis set type

Safety analysis

Subject analysis set description

Participants from the placebo arm identified as responders based on Week 10 assessments during the Induction Phase received placebo subcutaneously (SC) every 4 weeks from Weeks 14 to 26 during the 20 week double-blind extended treatment phase (ETP). At Week 30, participants underwent an assessment following which they were followed up until Week 42.

Subject analysis set title

GSK2831781 300 mg SC

Subject analysis set type

Safety analysis

Subject analysis set description

Participants from the GSK2831781 arms identified as responders based on Week 10 assessments during the Induction Phase received GSK2831781 300 mg SC every 4 weeks from Weeks 14 to 26 during the 20-week double-blind ETP. At Week 30, participants underwent an assessment following which they were followed up until Week 42.

Primary: Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Double-Blind Induction Phase

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End point title

Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Double-Blind Induction Phase ^[1]

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect or other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were collected up to Week 14 (for participants who later entered the Double Blind ETP) and Week 12 (for participants who later entered OL Induction Phase). Safety Population comprised of all participants who received at least one dose of study treatment.

End point type

Primary

End point timeframe

Up to a maximum of Week 14

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[2]	48 ^[3]	11 ^[4]	10 ^[5]	8 ^[6]
Units: Participants
AEs	10	27	6	2	2
SAEs	0	6	1	0	0

Notes
[2] - Safety Population
[3] - Safety Population
[4] - Safety Population
[5] - Safety Population
[6] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst-case vital signs results by potential clinical importance (PCI) criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

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End point title

Number of participants with worst-case vital signs results by potential clinical importance (PCI) criteria post-Baseline relative to Baseline-Double-Blind Induction Phase ^[7]

End point description

Vital signs were measured in a seated or semi-supine position after 5 minutes rest. Clinical concern range were: systolic blood pressure (SBP) (lower: <85 and upper: > 160 millimeters of mercury [mmHg]); diastolic blood pressure (DBP) (lower: <45 mmHg and upper: >100 mmHg); pulse rate (PR) (lower: <40 and upper: >110 beats per minute [bpm]) and temperature (Temp) (lower: <35 and upper: >38 degree Celsius). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To within (w/in) Range or No Change category. Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Primary

End point timeframe

Up to Week 10

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[8]	48 ^[9]	11 ^[10]	10 ^[11]	8 ^[12]
Units: Participants
DBP; To low; n=27, 47, 9, 8, 7	0	0	0	0	0
DBP; To w/in range or no change; n=27, 47, 9, 8, 7	27	47	9	8	7
DBP; To high; n=27, 47, 9, 8, 7	0	0	0	0	0
SBP; To low; n=27, 47, 10, 9, 6	0	0	1	0	0
SBP; To w/in range or no change; n=27, 47, 10, 9,6	26	45	9	9	6
SBP; To high; n=27, 47, 10, 9, 6	1	2	0	0	0
PR; To low; n=27, 47, 11, 9, 8	0	1	0	0	0
PR; To w/in range or no change; n=27, 47, 11, 9, 8	27	45	10	9	8
PR; To high; n=27, 47, 11, 9, 8	0	1	1	0	0
Temp; To low; n=26, 46, 11, 10, 7	0	0	0	0	0
Temp; To w/in range or no change; n=26,46,11,10,7	26	46	11	10	7
Temp; To high; n=26, 46, 11, 10, 7	0	0	0	0	0

Notes
[8] - Safety Population
[9] - Safety Population
[10] - Safety Population
[11] - Safety Population
[12] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

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End point title

Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase ^[13]

End point description

Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (Hct) (low: 0.201 and high: >0.599 proportion of red blood cells in blood); hemoglobin (Hgb) (low: <80 and high: >180 grams per liter [g/L]), lymphocytes (Lymph) (low: <0.8x10^9 cells/L); neutrophil (Neut) count (low: <1.5x10^9 cells/L); platelet (plat) count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); leukocytes (leuko) (low: <3x10^9 cells/L and high: >20x10^9cells/L) and eosinophils (Eos) (high: >=1x10^9 cells/L). Participants were counted in the worst-case category that their value changed to (low, w/in range or no change, or high), unless there was no change in their category. Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Primary

End point timeframe

Up to Week 10

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[14]	48 ^[15]	11 ^[16]	10 ^[17]	8 ^[18]
Units: Participants
Eos;w/in range or no change; n=25,45,9,8,7	24	44	9	8	7
Eos; To high; n=25,45,9,8,7	1	1	0	0	0
Hct; To low; n=24,43,7,6,7	0	0	0	0	0
Hct; To w/in range or no change; n=24,43,7,6,7	24	43	7	6	7
Hct; To high; n=24,43,7,6,7	0	0	0	0	0
Hgb; To low; n=24,45,5,7,7	0	0	1	1	0
Hgb; To w/in range or no change; n=24,45,5,7,7	24	45	4	6	7
Hgb; To high; n=24,45,5,7,7	0	0	0	0	0
Leuko; To low; n=27,43,8,9,6	0	2	0	1	0
Leuko; To w/in range or no change; n=27,43,8,9,6	27	41	8	8	6
Leuko; To high; n=27,43,8,9,6	0	0	0	0	0
Lymph; To low; n=26,45,8,8,8	1	6	1	3	2
Lymph; To w/in range or no change; n=26,45,8,8,8	25	39	7	5	6
Neut; To low; n=26,42,7,9,8	0	2	0	0	0
Neut; To w/in range or no change; n=26,42,7,9,8	26	40	7	9	8
Plat; To low; n=26,43,9,8,6	0	0	0	0	0
Plat; To w/in range or no change; n=26,43,9,8,6	25	41	9	7	6
Plat; To high; n=26,43,9,8,6	1	2	0	1	0

Notes
[14] - Safety Population
[15] - Safety Population
[16] - Safety Population
[17] - Safety Population
[18] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

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End point title

Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase ^[19]

End point description

Blood samples were collected for assessment of clinical chemistry parameters. Clinical concern range: albumin (Alb) (low: <30 and high: >55 g/L), calcium (Ca) (low: 2 and high: 2.75 millimoles per liter [mmol/L]), urea (high: >10.5 mmol/L); creatinine (Creat) (high: change from Baseline >26 micromoles per liter [µmol/L]), glucose (Glu) (low: <3.5 and high: >7.9 mmol/L); estimated glomerular filtration rate (eGFR) (low: <60 milliliters per minute per 1.73 square meter [mL/min/1.73m^2)]; potassium (Pot) (low: <3 and high: >5.5 mmol/L); sodium (Sod) (low: <130 and high: >150 mmol/L); protein (Pro) (low: <50 and high: >85 g/L) and C-reactive protein (CRP) (high: >30 milligrams/L). Participants were counted in worst-case category that their value changed to (low, w/in range or no change, or high), unless there was no change in their category. Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Primary

End point timeframe

Up to Week 10

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[20]	48 ^[21]	11 ^[22]	10 ^[23]	8 ^[24]
Units: Participants
Alb; To low; n=26,42,7,6,6	0	2	0	1	0
Alb; To w/in range or no change; n=26,42,7,6,6	26	40	7	5	6
Alb; To high; n=26,42,7,6,6	0	0	0	0	0
CRP; To w/in range or no change; n=26, 46,9,10,8	25	36	7	9	8
CRP; To high; n=26, 46,9,10,8	1	10	2	1	0
Cal; To low; n=26,45,7,4,7	1	0	0	1	0
Cal; To w/in range or no change; n=26,45,7,4,7	25	45	7	3	7
Cal; To high; n=26,45,7,4,7	0	0	0	0	0
eGFR; To low; n=24,46,6,9,7	1	1	0	1	0
eGFR; To w/in range or no change; n=24,46,6,9,7	23	45	6	8	7
Glu; To low; n=26,45,5,8,7	1	1	0	0	0
Glu; To w/in range or no change; n=26,45,5,8,7	25	43	5	8	7
Glu; To high; n=26,45,5,8,7	0	1	0	0	0
Pot; To low; n=27,44,10,7,8	0	1	0	0	0
Pot; To w/in range or no change; n=27,44,10,7,8	27	43	10	7	8
Pot; To high; n=27,44,10,7,8	0	0	0	0	0
Pro; To low; n=26,43,7,5,7	0	0	0	0	0
Pro To w/in range or no change; n=26,43,7,5,7	26	41	7	5	7
Pro; To high; n=26,43,7,5,7	0	2	0	0	0
Sod; To low; n=25,45,10,8,8	0	0	0	0	0
Sod; To w/in range or no change; n=25,45,10,8,8	25	45	10	8	8
Sod; To high; n=25,45,10,8,8	0	0	0	0	0
Urea; To w/in range or no change; n=26,45,5,6,7	26	45	5	6	7
Urea; To high; n=26,45,5,6,7	0	0	0	0	0
Creat; To w/in range or no change; n=27,44,9,6,7	27	44	9	6	7
Creat; To high; n=27,44,9,6,7	0	0	0	0	0

Notes
[20] - Safety Population
[21] - Safety Population
[22] - Safety Population
[23] - Safety Population
[24] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

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End point title

Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase ^[25]

End point description

Blood samples were collected for the assessment of liver function parameters. The clinical concern range for liver function parameters were: alanine aminotransferase (ALT) (high: >=2 times upper limit of normal [ULN]); aspartate aminotransferase (AST) (high: >=2 times ULN); alkaline phosphatase (ALP) (high: >=2 times ULN) and bilirubin (Bil) (high: >=1.5 times ULN). Participants were counted in the worst-case category that their value changed to (within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To within (w/in) Range or No Change category". Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Primary

End point timeframe

Up to Week 10

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[26]	48 ^[27]	11 ^[28]	10 ^[29]	8 ^[30]
Units: Participants
ALT; To low; n=26,44,7,7,8	0	0	0	0	0
ALT;To w/in range or no change; n=26,44,7,7,8	25	42	7	7	8
ALT; To high; n=26,44,7,7,8	1	2	0	0	0
AST; To low; n=26,45,7,8,7	0	0	0	0	0
AST; To w/in range or no change; n=26,45,7,8,7	26	44	7	8	7
AST; To high;n=26,45,7,8,7	0	1	0	0	0
ALP; To low; n=27,44,9,9,8	0	0	0	0	0
ALP; To w/in range or no change; n=27,44,9,9,8	27	44	9	9	8
ALP; To high; n=27,44,9,9,8	0	0	0	0	0
Bil; To low; n=25,45,9,8,8	0	0	0	0	0
Bil; To w/in range or no change; n=25,45,9,8,8	25	45	9	8	8
Bil; To high; n=25,45,9,8,8	0	0	0	0	0

Notes
[26] - Safety Population
[27] - Safety Population
[28] - Safety Population
[29] - Safety Population
[30] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

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End point title

Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase ^[31]

End point description

Urine samples were collected for the assessment of urine parameters by dipstick and microscopy. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample. The clinical concern range for urine parameters were: Bil (high: >1+), glu (high: >1+); ketone (ket) (high: >2+); leuko (high: >1+); leukocyte esterase (LE); nitrite (nit) (high: positive); occult blood (OB) (high: >1+); potential of hydrogen (pH) (low: <4.6 and high: >8); prot (high:>1+); erythrocytes (erythro) (high: >3 cells per high power field [hpf]); specific gravity (sp gra) (low: <1.001 and high: >1.035) and urobilinogen (uro) (high: >1 mg/deciliter). Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Primary

End point timeframe

Up to Week 10

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[32]	48 ^[33]	11 ^[34]	10 ^[35]	8 ^[36]
Units: Participants
Bil; To w/in range or no change; n=27,47,10,9,8	27	46	10	9	8
Bil; To high; n=27,47,10,9,8	0	1	0	0	0
Glu; To w/in range or no change; n=27,47,10,10,8	27	47	10	10	8
Glu; To high; n=27,47,10,10,8	0	0	0	0	0
Ket; To w/in range or no change; n=27,47,10,8,8	25	47	10	7	8
Ket; To high; n=27,47,10,8,8	2	0	0	1	0
LE; To w/in range or no change; n=26,45,9,8,8	25	37	9	8	8
LE; To high; n=26,45,9,8,8	1	8	0	0	0
Nit; To w/in range or no change; n=27,47,10,10,8	27	44	9	8	8
Nit; To high; n=27,47,10,10,8	0	3	1	2	0
OB; To w/in range or no change; n=26,46,9,10,8	24	42	9	10	8
OB; To high; n=26,46,9,10,8	2	4	0	0	0
pH; To low; n=27,46,9,10,7	0	0	0	0	0
pH; To w/in range or no change; n=27,46,9,10,7	26	46	9	10	7
pH; To high; n=27,46,9,10,7	1	0	0	0	0
Prot; To w/in range or no change; n=25,47,10,9,8	24	43	10	9	8
Prot; To high; n=25,47,10,9,8	1	4	0	0	0
Uro; To w/in range or no change; n=27,47,10,8,8	27	47	10	8	8
Uro; To high; n=27,47,10,8,8	0	0	0	0	0
Leuko; To w/in range or no change; n=9,18,2,3,1	8	15	1	3	1
Leuko; To high; n=9,18,2,3,1	1	3	1	0	0
Erythro; To w/in range or no change; n=9,18,2,3,1	9	16	1	3	1
Erythro; To high; n=9,18,2,3,1	0	2	1	0	0
Sp gra; To low; n=25,47,5,7,8	0	0	0	0	0
Sp gra; To w/in range or no change; n=25,47,5,7,8	21	44	5	7	8
Sp gra; To high; n=25,47,5,7,8	4	3	0	0	0

Notes
[32] - Safety Population
[33] - Safety Population
[34] - Safety Population
[35] - Safety Population
[36] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with maximum corrected QT (QTc) values post-Baseline relative to Baseline-Double-Blind Induction Phase

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End point title

Number of participants with maximum corrected QT (QTc) values post-Baseline relative to Baseline-Double-Blind Induction Phase ^[37]

End point description

Twelve lead electrocardiograms (ECGs) were obtained using an ECG machine that automatically calculated the QT interval corrected for heart rate according to either Bazett’s formula (QTcB) or Fridericia’s formula (QTcF). The clinical concern range for the QTcB and QTcF intervals was upper: >450 milliseconds. Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Primary

End point timeframe

Up to Week 10

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[38]	48 ^[39]	11 ^[40]	10 ^[41]	8 ^[42]
Units: Participants
QTcB; No change or decrease to <450; n=26,44,8,9,7	22	41	6	7	7
QTcB; Any increase to >=450; n=26,44,8,9,7	4	3	2	2	0
QTcF; No change or decrease to <450; n=26,46,7,9,7	26	45	7	8	7
QTcF; Any increase to >=450; n=26,46,7,9,7	0	1	0	1	0

Notes
[38] - Safety Population
[39] - Safety Population
[40] - Safety Population
[41] - Safety Population
[42] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in Complete 4-domain Mayo score at Week 10

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End point title

Change from Baseline in Complete 4-domain Mayo score at Week 10 ^[43]

End point description

Complete 4-domain Mayo Score is a 12-point scoring system where disease is evaluated based on 4 components: stool frequency, rectal bleeding, physician global assessment (PGA) and endoscopic appearance (with mild friability associated with an endoscopic score of 1). Score for each component ranges from 0 (normal/none) to 3 (severe). Complete Mayo score is calculated as sum of 4 components and ranges from 0 to 12. Higher scores indicate greater disease severity. Baseline value is latest pre-dose assessment with a non-missing value from Double-Blind Induction study phase. Change from Baseline=value at specified time point minus Baseline value. Intent-To-Treat-Exposed (ITTE) Population- all enrolled participants who received at least one dose of study treatment, and who had at least one valid post dose assessment. Only those participants with data available at the specified time points were analyzed.

End point type

Primary

End point timeframe

Baseline and Week 10

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[44]	36 ^[45]	4 ^[46]	2 ^[47]	3 ^[48]
Units: Scores on a scale
arithmetic mean (standard error)	-1.5 ( 0.45 )	-1.4 ( 0.36 )	-0.3 ( 0.48 )	-1.0 ( 2.00 )	-2.3 ( 0.33 )

Notes
[44] - ITTE Population
[45] - ITTE Population
[46] - ITTE Population
[47] - ITTE Population
[48] - ITTE Population

No statistical analyses for this end point

Secondary: Number of participants with AEs and SAEs-Double-Blind Extended Treatment Phase

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End point title

Number of participants with AEs and SAEs-Double-Blind Extended Treatment Phase

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect or other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. Safety Extended Treatment Population comprised of all participants who received at least one dose of study treatment in the Extended Treatment Phase

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	5 ^[49]	8 ^[50]
Units: Participants
AEs	1	3
SAEs	0	1

Notes
[49] - Safety Extended Treatment Population
[50] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with worst-case vital signs results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

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End point title

Number of participants with worst-case vital signs results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

End point description

Vital signs were measured in a seated or semi-supine position after 5 minutes rest. The clinical concern range for vital signs were: SBP (lower: <85 and upper: > 160 mmHg); DBP (lower: <45 mmHg and upper: >100 mmHg); PR (lower: <40 and upper: >110 bpm) and Temp (lower: <35 and upper: >38 degree Celsius). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To w/in Range or No Change category". Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	5 ^[51]	8 ^[52]
Units: Participants
DBP; To low	0	0
DBP; To w/in range or no change	5	8
DBP; To high	0	0
SBP; To low	0	0
SBP; To w/in range or no change	5	8
SBP; To high	0	0
PR; To low	0	0
PR; To w/in range or no change	5	8
PR; To high	0	0
Temp; To low	0	0
Temp; To w/in range or no change	5	8
Temp; To high	0	0

Notes
[51] - Safety Extended Treatment Population
[52] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

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End point title

Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

End point description

Blood samples were collected for the assessment of hematology parameters. Clinical concern range for the parameters were: Hct (low: 0.201 and high: >0.599 proportion of red blood cells in blood); Hgb (low: <80 and high: >180 g/L), Lymph (low: <0.8x10^9 cells/L); Neut count (low: <1.5x10^9 cells/L); plat count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); leuko (low: <3x10^9 cells/L and high: >20x10^9cells/L) and Eos (high: >=1x10^9 cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To w/in Range or No Change category". Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	5 ^[53]	8 ^[54]
Units: Participants
Eos;To w/in range or no change; n=4,8	4	8
Eos; To high; n=4,8	0	0
Hct; To low; n=5,8	0	0
Hct; To w/in range or no change; n=5,8	5	8
Hct; To high; n=5,8	0	0
Hgb; To low; n=5,8	0	0
Hgb; To w/in range or no change; n=5,8	5	8
Hgb; To high; n=5,8	0	0
Leuko; To low; n=5,8	0	0
Leuko; To w/in range or no change; n=5,8	5	8
Leuko; To high; n=5,8	0	0
Lymph; To low; n=5,8	0	2
Lymph; To w/in range or no change; n=5,8	5	6
Neut; To low; n=5,8	0	0
Neut; To w/in range or no change; n=5,8	5	8
Plat; To low; n=5,8	0	0
Plat; To w/in range or no change; n=5,8	5	6
Plat; To high; n=5,8	0	2

Notes
[53] - Safety Extended Treatment Population
[54] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

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End point title

Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

End point description

Blood samples were collected for the assessment of clinical chemistry parameters. Clinical concern range for the parameters were: Alb (low: <30 and high: >55 g/L), C) (low: 2 and high: 2.75 mmol/L), urea (high: >10.5 mmol/L); Creat (high: change from Baseline >26 µmol/L), Glu (low: <3.5 and high: >7.9 mmol/L); eGFR (low: <60 mL/min/1.73m^2]; Pot low: <3 and high: >5.5 mmol/L); Sod (low: <130 and high: >150 mmol/L); Pro (low: <50 and high: >85 g/L) and CRP (high: >30 milligrams/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To w/in Range or No Change category". Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	5 ^[55]	8 ^[56]
Units: Participants
Alb; To low; n=5,8	0	1
Alb; To w/in range or no change; n=5,8	5	7
Alb; To high; n=5,8	0	0
CRP; To w/in range or no change; n=5,8	5	6
CRP; To high; n=5,8	0	2
Cal; To low; n=5,8	0	0
Cal; To w/in range or no change; n=5,8	5	8
Cal; To high; n=5,8	0	0
eGFR; To low; n=4,8	0	1
eGFR; To w/in range or no change; n=4,8	4	7
Glu; To low; n=5,8	0	0
Glu; To w/in range or no change; n=5,8	5	8
Glu; To high; n=5,8	0	0
Pot; To low;n=4,8	0	0
Pot; To w/in range or no change; n=4,8	4	8
Pot; To high; n=4,8	0	0
Pro; To low; n=5,8	0	0
Pro To w/in range or no change; n=5,8	5	8
Pro; To high; n=5,8	0	0
Sod; To low; n=4,8	0	0
Sod; To w/in range or no change; n=4,8	4	8
Sod; To high; n=4,8	0	0
Urea; To w/in range or no change; n=5,8	5	8
Urea; To high; n=5,8	0	0
Creat; To w/in range or no change; n=5,8	5	8
Creat; To high; n=5,8	0	0

Notes
[55] - Safety Extended Treatment Population
[56] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Top of page

End point title

Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

End point description

Blood samples were collected for the assessment of liver function parameters. The clinical concern range for liver function parameters were: ALT (high: >=2 times ULN); AST (high: >=2 times ULN); ALP (high: >=2 times ULN) and Bil (high: >=1.5 times ULN). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To w/in Range or No Change category".

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	5 ^[57]	8 ^[58]
Units: Participants
ALT; To low	0	0
ALT;To w/in range or no change	5	8
ALT; To high	0	0
AST; To low	0	0
AST; To w/in range or no change	5	8
AST; To high	0	0
ALP; To low	0	0
ALP; To w/in range or no change	5	8
ALP; To high	0	0
Bil; To low	0	0
Bil; To w/in range or no change	5	8
Bil; To high	0	0

Notes
[57] - Safety Extended Treatment Population
[58] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

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End point title

Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

End point description

Urine samples were collected for the assessment of urine parameters by dipstick and microscopy. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample. The clinical concern range for urine parameters were: Bil (high: >1+), glu (high: >1+); ket (high: >2+); leuko (high: >1+); LE; nit (high: positive); OB (high: >1+); pH (low: <4.6 and high: >8); prot (high:>1+); erythro (high: >3 cells per hpf); sp gra (low: <1.001 and high: >1.035) and uro (high: >1 mg/deciliter). Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	5 ^[59]	8 ^[60]
Units: Participants
Bil; To w/in range or no change; n=5,8	5	8
Bil; To high; n=5,8	0	0
Glu; To w/in range or no change; n=5,8	5	8
Glu; To high; n=5,8	0	0
Ket; To w/in range or no change; n=5,8	5	8
Ket; To high; n=5,8	0	0
LE; To w/in range or no change; n=5,8	3	8
LE; To high; n=5,8	2	0
Nit; To w/in range or no change; n=5,8	5	7
Nit; To high; n=5,8	0	1
OB; To w/in range or no change; n=5,8	4	7
OB; To high; n=5,8	1	1
pH; To low; n=5,8	0	0
pH; To w/in range or no change; n=5,8	5	8
pH; To high; n=5,8	0	0
Prot; To w/in range or no change; n=5,8	4	8
Prot; To high; n=5,8	1	0
Uro; To w/in range or no change; n=5,8	5	8
Uro; To high; n=5,8	0	0
Leuko; To w/in range or no change; n=1,2	1	1
Leuko; To high; n=1,2	0	1
Erythro; To w/in range or no change; n=1,2	1	2
Erythro; To high; n=1,2	0	0
Sp gra; To low; n=5,8	0	0
Sp gra; To w/in range or no change; n=5,8	4	6
Sp gra; To high; n=5,8	1	2

Notes
[59] - Safety Extended Treatment Population
[60] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with maximum QTc values post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

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End point title

Number of participants with maximum QTc values post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

End point description

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the QTcB and QTcF intervals. The clinical concern range for the QTcB and QTcF intervals was upper: >450 milliseconds. Only those participants with data available at the specified timepoints were analyzed (indicated by n=X in category titles)

End point type

Secondary

End point timeframe

Week 14 to 30

End point values	Placebo SC	GSK2831781 300 mg SC
Number of subjects analysed	4 ^[61]	8 ^[62]
Units: Participants
QTcB; No change or decrease to <450; n=4,6	4	6
QTcB; Any increase to >=450; n=4,6	0	0
QTcF; No change or decrease to <450; n=3,6	3	6
QTcF; Any increase to >=450; n=3,6	0	0

Notes
[61] - Safety Extended Treatment Population
[62] - Safety Extended Treatment Population

No statistical analyses for this end point

Secondary: Number of participants with adapted Mayo endoscopic score of 0 or 1 at Week 10-Double-Blind Induction Phase

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End point title

Number of participants with adapted Mayo endoscopic score of 0 or 1 at Week 10-Double-Blind Induction Phase

End point description

The adapted Mayo clinical score consists of three components: stool frequency, rectal bleeding, and endoscopic appearance. The score for each component ranges from 0 (normal/none) to 3 (severe). The adapted Mayo endoscopic score of 0 indicates normal or inactive disease and 1 indicates mild disease (erythema, decreased vascular pattern). Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[63]	36 ^[64]	4 ^[65]	2 ^[66]	3 ^[67]
Units: Participants	4	3	0	0	0

Notes
[63] - ITTE Population
[64] - ITTE Population
[65] - ITTE Population
[66] - ITTE Population
[67] - ITTE Population

No statistical analyses for this end point

Secondary: Number of participants with adapted Mayo clinical remission at Week 10-Double-Blind Induction Phase

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End point title

Number of participants with adapted Mayo clinical remission at Week 10-Double-Blind Induction Phase

End point description

The adapted Mayo clinical score is based on the complete 4-domain Mayo clinical score, but without the PGA. It consists of three components: stool frequency, rectal bleeding, and mucosal endoscopic appearance. The score for each component ranges from 0 (normal/none) to 3 (severe). The total adapted Mayo score is calculated as the sum of all three components and ranges from 0 to 9. Higher scores indicate greater disease severity. Clinical remission is defined as adapted Mayo Clinical Score of <=2 with no individual sub-score >1 and a rectal bleeding sub score of 0 with stool frequency sub score not greater than Baseline. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[68]	36 ^[69]	4 ^[70]	2 ^[71]	3 ^[72]
Units: Participants	0	1	0	0	0

Notes
[68] - ITTE Population
[69] - ITTE Population
[70] - ITTE Population
[71] - ITTE Population
[72] - ITTE Population

No statistical analyses for this end point

Secondary: Number of participants with adapted Mayo clinical response at Week 10-Double-Blind Induction Phase

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End point title

Number of participants with adapted Mayo clinical response at Week 10-Double-Blind Induction Phase

End point description

The adapted Mayo clinical score is based on the complete 4-domain Mayo clinical score, but without the PGA. It consists of three components: stool frequency, rectal bleeding, and mucosal endoscopic appearance. The score for each component ranges from 0 (normal/none) to 3 (severe). The total adapted Mayo score is calculated as the sum of all three components and ranges from 0 to 9. Higher scores indicate greater disease severity. Clinical response is defined as reduction in adapted Mayo clinical score >=3 points from Baseline and >=30% from Baseline and decrease in the rectal bleeding sub-score of >=1 point from Baseline (or a score of 0 or 1). Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[73]	36 ^[74]	4 ^[75]	2 ^[76]	3 ^[77]
Units: Participants	5	6	0	1	0

Notes
[73] - ITTE Population
[74] - ITTE Population
[75] - ITTE Population
[76] - ITTE Population
[77] - ITTE Population

No statistical analyses for this end point

Secondary: Number of participants with symptomatic remission at Week 10-Double-Blind Induction Phase

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End point title

Number of participants with symptomatic remission at Week 10-Double-Blind Induction Phase

End point description

The Complete 4-domain Mayo Score is a 12-point scoring system where disease is evaluated based on the four components: stool frequency, rectal bleeding, PGA and endoscopic appearance (with mild friability associated with an endoscopic score of 1). Symptomatic remission is defined as a rectal bleeding subscore of 0, and a stool frequency subscore of <=1, with no worsening from Baseline. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[78]	36 ^[79]	4 ^[80]	2 ^[81]	3 ^[82]
Units: Participants	5	5	0	1	1

Notes
[78] - ITTE Population
[79] - ITTE Population
[80] - ITTE Population
[81] - ITTE Population
[82] - ITTE Population

No statistical analyses for this end point

Secondary: Change from Baseline in partial Mayo score over time-Double-Blind Induction Phase

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End point title

Change from Baseline in partial Mayo score over time-Double-Blind Induction Phase

End point description

The partial Mayo clinical score is based on the complete 4-domain Mayo clinical score but without the endoscopy sub-score. It consists of three components: stool frequency, rectal bleeding, and PGA. The score for each component ranges from 0 (normal/none) to 3 (severe). The total partial Mayo score is calculated as the sum of all three components and ranges from 0 to 9. Higher scores indicate greater disease severity. Baseline value was the latest pre-dose assessment with a non-missing value from Double-Blind Induction study phase. Change from Baseline was calculated as value at specified time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 2, 4, 6, and 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[83]	48 ^[84]	11 ^[85]	10 ^[86]	8 ^[87]
Units: Scores on a scale
arithmetic mean (standard error)
Week 2; n=27, 47, 11, 10, 8	-0.8 ( 0.33 )	-0.6 ( 0.22 )	-1.0 ( 0.50 )	0.5 ( 0.54 )	-1.3 ( 0.65 )
Week 4; n=26, 46, 8, 8, 7	-1.0 ( 0.31 )	-0.7 ( 0.28 )	-1.4 ( 0.60 )	-0.4 ( 0.18 )	-1.7 ( 0.52 )
Week 6; n=24, 44, 8, 6, 8	-1.3 ( 0.40 )	-0.8 ( 0.31 )	-1.0 ( 0.53 )	-0.8 ( 0.31 )	-2.6 ( 0.53 )
Week 10; n=22, 39, 4, 4, 4	-1.1 ( 0.44 )	-1.0 ( 0.32 )	0.3 ( 0.48 )	-1.0 ( 0.41 )	-2.0 ( 0.41 )

Notes
[83] - ITTE Population
[84] - ITTE Population
[85] - ITTE Population
[86] - ITTE Population
[87] - ITTE Population

No statistical analyses for this end point

Secondary: Change from Baseline in adapted Mayo endoscopy score at Week 10-Double-Blind Induction Phase

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End point title

Change from Baseline in adapted Mayo endoscopy score at Week 10-Double-Blind Induction Phase

End point description

The adapted Mayo clinical score is based on the complete 4-domain Mayo clinical score, but without the PGA. It consists of three components: stool frequency, rectal bleeding, and mucosal endoscopic appearance. The total adapted Mayo endoscopy score ranges from 0 (normal or inactive disease) to 3 (severe disease [spontaneous bleeding, ulceration]). Baseline value was the latest pre-dose assessment with a non-missing value from Double-Blind Induction study phase. Change from Baseline was calculated as value at specified time point minus Baseline value. Only those participants with data available at the specified time points were analyzed

End point type

Secondary

End point timeframe

Baseline and Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[88]	36 ^[89]	4 ^[90]	2 ^[91]	3 ^[92]
Units: Scores on a scale
arithmetic mean (standard error)	-0.2 ( 0.14 )	-0.1 ( 0.12 )	0.0 ( 0.00 )	0.5 ( 0.50 )	-0.3 ( 0.33 )

Notes
[88] - ITTE Population
[89] - ITTE Population
[90] - ITTE Population
[91] - ITTE Population
[92] - ITTE Population

No statistical analyses for this end point

Secondary: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) at Week 10-Double-Blind Induction Phase

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End point title

Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) at Week 10-Double-Blind Induction Phase

End point description

UCEIS was used as an additional tool to assess disease activity based on 3 sub-scales: endoscopic vascular pattern, bleeding, erosions and ulcerations. Individual sub-scale scores were vascular pattern (0=Normal, 1=Patchy loss, 2=Obliterated); bleeding (0=None, 1=Mucosal, 2=Luminal mild, 3=Luminal severe); erosions and ulcerations (0=None, 1=Erosions, 2=Superficial ulcer, 3=Deep ulcer). UCEIS total score was calculated as the sum of all 3 sub-scale scores and ranges from 0 to 8, with higher scores indicating more severe disease. Baseline value was the latest pre-dose assessment with a non-missing value from Double-Blind Induction study phase. Change from Baseline was calculated as value at specified time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[93]	36 ^[94]	4 ^[95]	2 ^[96]	3 ^[97]
Units: Scores on a scale
arithmetic mean (standard error)	-0.1 ( 0.41 )	-0.0 ( 0.25 )	0.5 ( 0.65 )	1.0 ( 0.00 )	0.0 ( 0.58 )

Notes
[93] - ITTE Population
[94] - ITTE Population
[95] - ITTE Population
[96] - ITTE Population
[97] - ITTE Population

No statistical analyses for this end point

Secondary: Rate of Robarts Histopathology Index (RHI) remission at Week 10-Double-Blind Induction Phase

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End point title

Rate of Robarts Histopathology Index (RHI) remission at Week 10-Double-Blind Induction Phase

End point description

RHI was assessed by central reading of gut pinch biopsies. The RHI Score is a continuous score, ranging from 0-33 with higher scores indicating more severe disease. RHI Remission is defined as an RHI score <= 6. Median and 95% equal tailed credible intervals constructed using a Beta-Binomial model with an uninformative Beta(1/3, 1/3) prior are presented. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[98]	36 ^[99]	4 ^[100]	2 ^[101]	3 ^[102]
Units: Percentage of participants
median (confidence interval 95%)	19.1 (6.4 to 38.8)	13.9 (5.3 to 27.5)	2.4 (0.0 to 39.4)	4.6 (0.0 to 62.7)	3.1 (0.0 to 48.5)

Notes
[98] - ITTE Population
[99] - ITTE Population
[100] - ITTE Population
[101] - ITTE Population
[102] - ITTE Population

No statistical analyses for this end point

Secondary: Rate of Nancy Histological Index remission at Week 10-Double-Blind Induction Phase

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End point title

Rate of Nancy Histological Index remission at Week 10-Double-Blind Induction Phase

End point description

Nancy Histological Index was assessed by central reading of gut pinch biopsies. Key domains for scoring of the indices include chronic inflammatory infiltrate; neutrophils in the epithelium, lamina propria neutrophils, erosion and ulceration scored from 0 to 3 and multiplied by a weighting factor. The total Nancy Histological Index score is calculated by summing the weighted scores of the histological items, with total scores ranging from 0 (no disease activity) to 33 (severe disease activity). Nancy Index Remission was defined as a grade of 0 or 1. Median and 95% equal tailed credible intervals constructed using a Beta-Binomial model with an uninformative Beta(1/3, 1/3) prior are presented. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[103]	36 ^[104]	4 ^[105]	2 ^[106]	3 ^[107]
Units: Percentage of participants
median (confidence interval 95%)	19.1 (6.4 to 38.8)	11.1 (3.6 to 23.9)	2.4 (0.0 to 39.4)	4.6 (0.0 to 62.7)	3.1 (0.0 to 48.5)

Notes
[103] - ITTE Population
[104] - ITTE Population
[105] - ITTE Population
[106] - ITTE Population
[107] - ITTE Population

No statistical analyses for this end point

Secondary: Rate of Geboes Histological Index remission at Week 10-Double-Blind Induction Phase

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End point title

Rate of Geboes Histological Index remission at Week 10-Double-Blind Induction Phase

End point description

The Geboes Index is divided in 6 grades: architectural changes [grade 0], chronic inflammatory infiltrate [grade 1], lamina propria neutrophils and eosinophils [grade 2], neutrophils in epithelium [grade 3], crypt destruction [grade 4] and erosions or ulcerations [grade 5]. The subscores for grade 0 to 4 ranges from 0 (none/no abnormality) to 3 (marked increase/severe abnormality) and for grade 5 ranges from 0 (No erosion, ulceration, or granulation tissue) to 4 (Ulcer or granulation tissue). The overall Geboes score is derived by summing the subscores of the grades and ranges from 0 to 22, with higher scores indicating greater disease severity. Geboes Histological Remission will be defined as a Geboes score <2. Median and 95% equal tailed credible intervals constructed using a Beta-Binomial model with an uninformative Beta(1/3, 1/3) prior are presented. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	21 ^[108]	36 ^[109]	4 ^[110]	2 ^[111]	3 ^[112]
Units: Percentage of participants
median (confidence interval 95%)	4.8 (0.4 to 19.2)	2.8 (0.2 to 11.6)	2.4 (0.0 to 39.4)	4.6 (0.0 to 62.7)	3.1 (0.0 to 48.5)

Notes
[108] - ITTE Population
[109] - ITTE Population
[110] - ITTE Population
[111] - ITTE Population
[112] - ITTE Population

No statistical analyses for this end point

Secondary: Change from Baseline in serum CRP level over time-Double-Blind Induction Phase

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End point title

Change from Baseline in serum CRP level over time-Double-Blind Induction Phase

End point description

Serum samples were collected at indicated time points to measure CRP levels. Baseline value was the latest pre-dose assessment with a non-missing value from Double-Blind Induction study phase. Change from Baseline was calculated as value at specified time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 2, 4, 6, and 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[113]	48 ^[114]	11 ^[115]	10 ^[116]	8 ^[117]
Units: Milligrams per liter
arithmetic mean (standard deviation)
Week 2; n=27, 47, 11, 10, 8	-1.52 ( 8.508 )	1.01 ( 8.004 )	8.23 ( 16.881 )	25.14 ( 62.574 )	-7.71 ( 14.627 )
Week 4; n=26,45,7,7,7	-3.38 ( 8.188 )	6.73 ( 21.625 )	0.74 ( 3.376 )	26.23 ( 62.003 )	-9.41 ( 18.059 )
Week 6; n=24,45,8,6,8	-3.09 ( 6.748 )	4.45 ( 13.491 )	2.34 ( 7.016 )	12.20 ( 15.566 )	-8.16 ( 18.602 )
Week 10; n=22,39,4,4,4	2.89 ( 9.460 )	8.99 ( 21.549 )	8.40 ( 8.102 )	6.75 ( 13.749 )	-8.48 ( 20.407 )

Notes
[113] - ITTE Population
[114] - ITTE Population
[115] - ITTE Population
[116] - ITTE Population
[117] - ITTE Population

No statistical analyses for this end point

Secondary: Ratio to Baseline in fecal calprotectin over time-Double-Blind Induction Phase

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End point title

Ratio to Baseline in fecal calprotectin over time-Double-Blind Induction Phase

End point description

Fecal samples were collected at indicated time points to measure fecal calprotectin. Baseline value was the latest pre-dose assessment with a non-missing value from Double-Blind Induction study phase. Ratio to Baseline is the value at specified time point divided by Baseline value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates data was not available as insufficient participants were analyzed.

End point type

Secondary

End point timeframe

Baseline and Weeks 2, 4, 6, and 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[118]	48 ^[119]	11 ^[120]	10 ^[121]	8 ^[122]
Units: Ratio
geometric mean (geometric coefficient of variation)
Week 2; n=25,40,9,9,6	1.28 ( 311.68 )	0.90 ( 504.70 )	0.57 ( 206.90 )	2.05 ( 565.80 )	0.57 ( 200.43 )
Week 4; n=3,2,0,2,0	0.28 ( 296.27 )	1.58 ( 794.82 )	99999 ( 99999 )	1.60 ( 55.72 )	99999 ( 99999 )
Week 6; n=23,37,7,6,7	0.99 ( 688.97 )	0.99 ( 576.84 )	4.01 ( 8478.60 )	3.42 ( 477.17 )	2.51 ( 182.31 )
Week 10; n=20,31,3,3,4	1.68 ( 217.05 )	1.27 ( 961.25 )	3.82 ( 76.67 )	8.50 ( 2110.12 )	0.50 ( 251.03 )

Notes
[118] - ITTE Population
[119] - ITTE Population
[120] - ITTE Population
[121] - ITTE Population
[122] - ITTE Population

No statistical analyses for this end point

Secondary: Area under the concentration-time curve over the 1st dosing interval (AUC[0-tau]) for GSK2831781 following SC dosing in Double-Blind Extended Treatment Phase

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End point title

Area under the concentration-time curve over the 1st dosing interval (AUC[0-tau]) for GSK2831781 following SC dosing in Double-Blind Extended Treatment Phase

End point description

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK2831781. PK parameters were calculated using standard non-compartmental analysis. Pharmacokinetic Double-Blind Extended Population comprised of all participants in the Safety Extended Treatment Phase population who had at least 1 non-missing PK assessment in the Extended Treatment phase. Only those participants with data at more than two of the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 14 (pre-dose, 24, 72 and 168 hours post-dose); Week 18 (pre-dose and early withdrawal post-dose)

End point values	GSK2831781 300 mg SC
Number of subjects analysed	3 ^[123]
Units: Hours*micrograms per milliliter
geometric mean (geometric coefficient of variation)	24336.92 ( 23.797 )

Notes
[123] - Pharmacokinetic Double-Blind Extended Population

No statistical analyses for this end point

Secondary: Maximum concentration (Cmax) of GSK2831781 observed following 1st SC dosing in Double-Blind Extended Treatment Phase

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End point title

Maximum concentration (Cmax) of GSK2831781 observed following 1st SC dosing in Double-Blind Extended Treatment Phase

End point description

Blood samples were collected at indicated time points for PK analysis of GSK2831781. PK parameters were calculated using standard non-compartmental analysis. Only those participants with data at more than two of the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 14 (pre-dose, 24, 72 and 168 hours post-dose); Week 18 (pre-dose and early withdrawal post-dose)

End point values	GSK2831781 300 mg SC
Number of subjects analysed	3 ^[124]
Units: Micrograms per milliliter
geometric mean (geometric coefficient of variation)	55.64 ( 13.374 )

Notes
[124] - Pharmacokinetic Double-Blind Extended Population

No statistical analyses for this end point

Secondary: Time at which the maximum concentration is observed (tmax) for GSK2831781 following 1st SC dosing in Double-Blind Extended Treatment Phase

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End point title

Time at which the maximum concentration is observed (tmax) for GSK2831781 following 1st SC dosing in Double-Blind Extended Treatment Phase

End point description

End point type

Secondary

End point timeframe

Week 14 (pre-dose, 24, 72 and 168 hours post-dose); Week 18 (pre-dose and early withdrawal post-dose)

End point values	GSK2831781 300 mg SC
Number of subjects analysed	3 ^[125]
Units: Hours
median (full range (min-max))	72.03 (24.3 to 170.0)

Notes
[125] - Pharmacokinetic Double-Blind Extended Population

No statistical analyses for this end point

Secondary: Number of participants with positive anti-drug antibodies at each visit-Double-Blind Induction Phase

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End point title

Number of participants with positive anti-drug antibodies at each visit-Double-Blind Induction Phase

End point description

Serum samples were assessed for the presence of anti-drug antibodies using a tiered approach. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'confirmed positive'. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates data was not available as insufficient participants were analyzed.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 6, and 10

End point values	Placebo IV	GSK2831781 450 mg IV	GSK2831781 300 mg IV	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Number of subjects analysed	27 ^[126]	48 ^[127]	11 ^[128]	10 ^[129]	8 ^[130]
Units: Participants
Baseline; n=27,48,11,10,8	0	0	0	0	0
Week 2; n=27,47,11,10,8	0	0	0	0	0
Week 4; n=25,46,7,7,7	0	0	0	0	0
Week 6; n=1,3,3,0,3	0	0	0	99999	0
Week 10; n=22,39,4,4,4	0	0	0	0	0

Notes
[126] - Safety Population
[127] - Safety Population
[128] - Safety Population
[129] - Safety Population
[130] - Safety Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to Week 12 (participants who entered OL induction phase) or Week 14 (participants who entered double-blind [DB] ETP) for DB induction phase, from Week 14 to 30 for DB ETP, from Week 12 to 22 for OL induction phase and from Week 22 to 42 for OL ETP

Adverse event reporting additional description

Non-SAEs and SAEs were collected in Safety Population for Double-blind induction phase, Safety ETP for double-blind ETP, Safety OL induction and Safety OL ETP for OL induction phase and OL ETP respectively.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

GSK2831781 450 mg IV

Reporting group description

Participants were administered GSK2831781 450 milligrams (mg) via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy.

Reporting group title

Placebo IV

Reporting group description

Participants were administered placebo via the intravenous (IV) route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy.

Reporting group title

GSK2831781 300 mg IV

Reporting group description

Participants were administered GSK2831781 300 mg via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy.

Reporting group title

GSK2831781 300 mg SC

Reporting group description

Reporting group title

Open-label GSK2831781 450 mg IV

Reporting group description

Participants identified as non-responders during the double-blind Induction phase at Week 10 were administered GSK2831781 450 mg IV on Weeks 12, 14, 18 and 22 during the open-label (OL) induction phase.

Reporting group title

Placebo SC

Reporting group description

Reporting group title

Open-label GSK2831781 300 mg SC

Reporting group description

Participants from the Open-label induction phase who responded at Week 22 entered the 20-week (Week 22 to Week 42) open-label extended treatment phase and received GSK2831781 300 mg SC every 4 weeks from Week 26 until Week 38. Participants were followed up until Week 54.

Reporting group title

GSK2831781 150 mg IV

Reporting group description

Participants were administered GSK2831781 150 mg via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy.

Reporting group title

GSK2831781 45 mg IV

Reporting group description

Participants were administered GSK2831781 45 mg via the IV route on Day 1, Weeks 2, 6 and 10. At Week 10, participants underwent Induction assessment including endoscopy.

Serious adverse events	GSK2831781 450 mg IV	Placebo IV	GSK2831781 300 mg IV	GSK2831781 300 mg SC	Open-label GSK2831781 450 mg IV	Placebo SC	Open-label GSK2831781 300 mg SC	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 48 (12.50%)	0 / 27 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	3 / 42 (7.14%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 48 (6.25%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis ulcerative
subjects affected / exposed	4 / 48 (8.33%)	0 / 27 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	2 / 42 (4.76%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	1 / 1	0 / 1	0 / 2	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	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	GSK2831781 450 mg IV	Placebo IV	GSK2831781 300 mg IV	GSK2831781 300 mg SC	Open-label GSK2831781 450 mg IV	Placebo SC	Open-label GSK2831781 300 mg SC	GSK2831781 150 mg IV	GSK2831781 45 mg IV
Total subjects affected by non serious adverse events
subjects affected / exposed	26 / 48 (54.17%)	10 / 27 (37.04%)	6 / 11 (54.55%)	3 / 8 (37.50%)	18 / 42 (42.86%)	1 / 5 (20.00%)	2 / 7 (28.57%)	2 / 10 (20.00%)	2 / 8 (25.00%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	0	0	0	0	0	0	0	1
Phlebitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Haematoma
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Pelvic venous thrombosis
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Thrombosed varicose vein
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Pain
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Asthenia
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Peripheral swelling
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	0	0	0	0	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	3 / 48 (6.25%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	3	0	0	0	1	0	0	0	0
Pulmonary mass
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Psychiatric disorders
Mixed anxiety and depressive disorder
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Somatic symptom disorder
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Depressed mood
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Investigations
Heart rate decreased
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	2 / 48 (4.17%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0
Body temperature increased
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Glucose urine present
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Myocardial fibrosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Arrhythmia
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	4 / 48 (8.33%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 42 (4.76%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	6	0	0	0	2	0	0	0	0
Migraine
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	4 / 42 (9.52%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	1	0	4	0	0	0	0
Thrombocytosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0
Leukopenia
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 48 (2.08%)	1 / 27 (3.70%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	1	1	0	1	0	0	0	0
Ear pain
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Eye disorders
Blepharitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Vitreous floaters
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Colitis ulcerative
subjects affected / exposed	12 / 48 (25.00%)	1 / 27 (3.70%)	2 / 11 (18.18%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	1 / 7 (14.29%)	2 / 10 (20.00%)	0 / 8 (0.00%)
occurrences all number	13	1	2	0	1	0	1	2	0
Dental caries
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Malabsorption
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0
Nausea
subjects affected / exposed	2 / 48 (4.17%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	1	0	0	1	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Dyspepsia
subjects affected / exposed	2 / 48 (4.17%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Frequent bowel movements
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hepatobiliary disorders
Hepatitis toxic
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pyoderma gangrenosum
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthropathy
subjects affected / exposed	2 / 48 (4.17%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	1 / 8 (12.50%)
occurrences all number	2	0	0	0	0	0	0	0	1
Arthritis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	1
Myalgia
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Arthralgia
subjects affected / exposed	1 / 48 (2.08%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	3 / 48 (6.25%)	1 / 27 (3.70%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	3	1	1	0	1	0	0	0	0
Nasopharyngitis
subjects affected / exposed	2 / 48 (4.17%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 10 (10.00%)	0 / 8 (0.00%)
occurrences all number	2	0	1	0	1	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	1 / 48 (2.08%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	1	0	0	0	0	0	0	1
Herpes zoster
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Urinary tract infection
subjects affected / exposed	2 / 48 (4.17%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	2	0	0	0	0
Suspected COVID-19
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 42 (4.76%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Tinea pedis
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Nasal herpes
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 48 (0.00%)	0 / 27 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0
Iron deficiency
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 42 (4.76%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	0
Decreased appetite
subjects affected / exposed	1 / 48 (2.08%)	0 / 27 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 48 (0.00%)	1 / 27 (3.70%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 10 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

17 Jan 2019

Amendment 1: Changes requested by Medicines and Healthcare products Regulatory Agency (MHRA)

10 Sep 2019

Amendment 2: Exclusion criteria adapted to allow participants following inadequate response, loss of response, or intolerance to up to three classes of approved advanced therapies for ulcerative colitis. Amalgamation of comments from regulatory authorities. Incorporation of stratification for Japanese ethnicity, and Protocol clarifications and corrections

03 Sep 2020

Amendment 3: Provision for home healthcare (home nursing and telemedicine) approaches for selected study visits where applicable country and local regulations and infrastructure allow. Clarification of COVID-19 specific measures. Correction of protocol inconsistencies and clarification of study procedures and objectives, including the time frame of the collection of safety data in the induction period (primary endpoint). Estimands have been introduced following best practice and the term ‘evaluable’ has been removed for consistency. The study retains the principle that if more participants (of those required for the hypothetical estimand) drop out than has been planned for, then additional participants may be recruited. The primary analysis will now fit the originally planned dose-response model using a Bayesian framework with non-informative priors. This allows consistency in estimation across endpoints, including when data are missing, but does not change the sample size required.

12 Nov 2020

Amendment 4: Main changes: Response to Health Authority feedback following review of Protocol Amendment 3, regarding the first SC dose administration and post dose monitoring. Minor changes: clarification for investigators and administrative corrections

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Double-Blind Induction Phase

Primary: Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Double-Blind Induction Phase

Primary: Number of participants with worst-case vital signs results by potential clinical importance (PCI) criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case vital signs results by potential clinical importance (PCI) criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with maximum corrected QT (QTc) values post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Number of participants with maximum corrected QT (QTc) values post-Baseline relative to Baseline-Double-Blind Induction Phase

Primary: Change from Baseline in Complete 4-domain Mayo score at Week 10

Primary: Change from Baseline in Complete 4-domain Mayo score at Week 10

Secondary: Number of participants with AEs and SAEs-Double-Blind Extended Treatment Phase

Secondary: Number of participants with AEs and SAEs-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case vital signs results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case vital signs results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case hematology results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case clinical chemistry results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case liver function results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with worst-case urinalysis results by PCI criteria post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with maximum QTc values post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with maximum QTc values post-Baseline relative to Baseline-Double-Blind Extended Treatment Phase

Secondary: Number of participants with adapted Mayo endoscopic score of 0 or 1 at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with adapted Mayo endoscopic score of 0 or 1 at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with adapted Mayo clinical remission at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with adapted Mayo clinical remission at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with adapted Mayo clinical response at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with adapted Mayo clinical response at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with symptomatic remission at Week 10-Double-Blind Induction Phase

Secondary: Number of participants with symptomatic remission at Week 10-Double-Blind Induction Phase

Secondary: Change from Baseline in partial Mayo score over time-Double-Blind Induction Phase

Secondary: Change from Baseline in partial Mayo score over time-Double-Blind Induction Phase

Secondary: Change from Baseline in adapted Mayo endoscopy score at Week 10-Double-Blind Induction Phase

Secondary: Change from Baseline in adapted Mayo endoscopy score at Week 10-Double-Blind Induction Phase

Secondary: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) at Week 10-Double-Blind Induction Phase

Secondary: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) at Week 10-Double-Blind Induction Phase

Secondary: Rate of Robarts Histopathology Index (RHI) remission at Week 10-Double-Blind Induction Phase

Secondary: Rate of Robarts Histopathology Index (RHI) remission at Week 10-Double-Blind Induction Phase

Secondary: Rate of Nancy Histological Index remission at Week 10-Double-Blind Induction Phase

Secondary: Rate of Nancy Histological Index remission at Week 10-Double-Blind Induction Phase

Secondary: Rate of Geboes Histological Index remission at Week 10-Double-Blind Induction Phase

Secondary: Rate of Geboes Histological Index remission at Week 10-Double-Blind Induction Phase

Secondary: Change from Baseline in serum CRP level over time-Double-Blind Induction Phase

Secondary: Change from Baseline in serum CRP level over time-Double-Blind Induction Phase

Secondary: Ratio to Baseline in fecal calprotectin over time-Double-Blind Induction Phase

Secondary: Ratio to Baseline in fecal calprotectin over time-Double-Blind Induction Phase

Secondary: Area under the concentration-time curve over the 1st dosing interval (AUC[0-tau]) for GSK2831781 following SC dosing in Double-Blind Extended Treatment Phase

Secondary: Area under the concentration-time curve over the 1st dosing interval (AUC[0-tau]) for GSK2831781 following SC dosing in Double-Blind Extended Treatment Phase

Secondary: Maximum concentration (Cmax) of GSK2831781 observed following 1st SC dosing in Double-Blind Extended Treatment Phase

Secondary: Maximum concentration (Cmax) of GSK2831781 observed following 1st SC dosing in Double-Blind Extended Treatment Phase

Secondary: Time at which the maximum concentration is observed (tmax) for GSK2831781 following 1st SC dosing in Double-Blind Extended Treatment Phase

Secondary: Time at which the maximum concentration is observed (tmax) for GSK2831781 following 1st SC dosing in Double-Blind Extended Treatment Phase

Secondary: Number of participants with positive anti-drug antibodies at each visit-Double-Blind Induction Phase

Secondary: Number of participants with positive anti-drug antibodies at each visit-Double-Blind Induction Phase

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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