A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02683785
• Collaborator: (none)
• Enrollment: 44
• Locations: 16
• Arms: 2
• Actual Duration (Months): 20.4
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a randomized, Phase IIa, multicentre, double-blind, placebo-controlled parallel group study with the primary objective to assess the efficacy potential of GSK3196165 on pain, in subjects with active inflammatory hand osteoarthritis (HOA).

Approximately 40 subjects will be enrolled into the study, following a screening period of up to 4 weeks. The total treatment period will be 12 weeks, with the follow up period completing at Week 22. At least 40 subjects will be randomized across the two treatment arms, to either placebo or GSK3196165 in a 1:1 ratio.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: GSK3196165; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-centre Phase IIa Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK3196165 in Subjects With Inflammatory Hand Osteoarthritis
• Actual Study Start Date: Mar 17, 2016
• Actual Primary Completion Date: Nov 29, 2017
• Actual Study Completion Date: Nov 29, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK3196165 Subjects will receive a total of 8 doses of GSK3196165 over a 12-week treatment period.	Drug: GSK3196165; GSK3196165 will be supplied as a liquid and will be administered as a subcutaneous injection. The drug will be administered weekly for 5 injections, then every other week for 3 further injections.
Placebo Comparator: Placebo Subjects will receive a total of 8 doses of placebo over a 12-week treatment period.	Drug: Placebo; Matching placebo will be administered as above.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6 [Baseline (Day 1 Pre-dose) and Week 6]

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

Secondary Outcome Measures

1. Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit [Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

   Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score is calculated by sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.

2. Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit [Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12]

   Participants were required to complete a daily pain NRS based on their 24-hour worst hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The score is calculated as sum of daily 24 hours worst hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.

3. Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit [Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)]

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

4. Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit [Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)]

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

5. Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit [Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)]

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

6. Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit [Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)]

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

7. Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. [Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12]

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

8. Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit [Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12]

   Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

9. Change From Baseline in Number of Tender Hand Joints at Each Visit [Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12]

   Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored >0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

10. Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity [Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12]

    Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

11. Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity [Baseline, Weeks 2, 4, 8, and 12]

    Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

12. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Up to Week 22]

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

13. Number of Participants With Infections [Up to Week 22]

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

14. Number of Participants With Pulmonary Events [Up to Week 22]

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

15. Number of Participants With Anti-GSK3196165 Binding Antibodies [Up to Week 22]

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

16. Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165 [Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22]

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

17. Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165 [Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22]

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

18. Absoption Rate Constant (Ka) of GSK3196165 [Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22]

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

19. Serum Concentration of GSK3196165 by Visit [Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)]

    Blood samples were collected at indicated time points for pharmacokinetic analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age >=18 years at the time of signing informed consent.

• Meets American College of Rheumatology (ACR) classification of osteoarthritis (OA) and have not responded to analgesics (level 1 and 2) or to non-steroidal anti-inflammatory drugs (NSAIDs) for at least 10 days in the past 3 months.

• Active disease at screening and randomization with at least two swollen and tender proximal interphalangeal (PIP) and/or distal interphalangeal (DIP) joints in the affected hand.

• Signs of inflammation such as synovitis in the MRI scan of the affected hand.

• Must have a subject's self assessment of 24-hour average hand pain intensity at baseline of at least '5' on an 11-point Numerical Rating Scale (NRS, 0-10).

• Weight >=45 kilogram (kg).

• Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria.

• Diffusing capacity of the lung for carbon monoxide (DLCO) >=70% predicted; forced expiratory volume in 1 second (FEV1) >=80% predicted.

• No evidence of active or latent infection with Mycobacterium tuberculosis (TB).

Exclusion Criteria:

• Pregnant or lactating women.

• History of any clinically significant inflammatory disease other than inflammatory HOA, especially, but not limited to, rheumatoid arthritis or spondylarthropathies.

• Diagnosis of rheumatoid arthritis, fibromyalgia, gout, calcium pyrophosphate deposition disease (CPPD), pseudogout, hemochromatosis or other inflammatory rheumatological or autoimmune disorders.

• Clinical suspicion of, or previous investigation for CPPD or pseudogout, or history of chondrocalcinosis.

• Any injury, medical or surgical procedure to the affected joint(s) that may interfere with evaluation of the target HOA joint(s).

• History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.

• Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration of the study or follow-up period.

• History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary alveolar proteinosis [PAP]).

• Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained.

• Significant unstable or uncontrolled acute or chronic disease which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.

• A history of malignancy.

• Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.

• Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2 infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Miami	Florida	United States	33015
2	GSK Investigational Site	Duncansville	Pennsylvania	United States	16635
3	GSK Investigational Site	Erlangen	Bayern	Germany	91054
4	GSK Investigational Site	Fulda	Hessen	Germany	36043
5	GSK Investigational Site	Rendsburg	Schleswig-Holstein	Germany	24768
6	GSK Investigational Site	Enschede		Netherlands	7511JX
7	GSK Investigational Site	Rotterdam		Netherlands	3015 CE
8	GSK Investigational Site	Sneek		Netherlands	8601 ZK
9	GSK Investigational Site	Bialystok		Poland	15-879
10	GSK Investigational Site	Nowa Sol		Poland	67-100
11	GSK Investigational Site	Warszawa		Poland	00-660
12	GSK Investigational Site	Warszawa		Poland	03-291
13	GSK Investigational Site	Canterbury	Kent	United Kingdom	CT1 3NG
14	GSK Investigational Site	Derby		United Kingdom	DE22 3NE
15	GSK Investigational Site	North Shields		United Kingdom	NE298NH
16	GSK Investigational Site	York		United Kingdom	YO31 8HE

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jan 3, 2017
• Statistical Analysis Plan - Feb 9, 2018

More Information

Publications

• Georg Schett, Chris Bainbridge, Mario Berkowitz, Katherine Davy, Sofia Fernandes, Eduard Griep, Stephen Harrison, James Lloyd-Hughes, Alexandra Morgan-Roberts, Mark Layton, Nonna Anna Nowak, Jatin Patel, Jürgen Rech, Sarah Watts, Paul P. Tak. A Phase IIa, randomised study of the safety, pharmacokinetics, pharmacodynamics and clinical activity of the anti-GM-CSF antibody GSK3196165 in patients with hand osteoarthritis. Lancet Rheumatol. 2020; DOI: 10.1016/S2665-9913(20)30171-5

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02683785
• Other Study ID Numbers: 204851; 2015-003089-96
• First Posted: Feb 17, 2016
• Last Update Posted: Jan 11, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Pain intensity; Hand Osteoarthritis; GSK3196165; AUSCAN; GM-CSF; Numerical Rating Scale
• Additional relevant MeSH terms: Osteoarthritis

Study Results

Participant Flow

Recruitment Details	This was a multi-center, double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in participants with inflammatory hand osteoarthritis. The study was conducted in five countries in Poland, United Kingdom, Netherlands, Germany and United States.
Pre-assignment Detail	A total 121 participants were screened of which 77 were screen failures and 44 participants were enrolled in the study.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Period Title: Overall Study
STARTED	22	22
COMPLETED	21	18
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	Placebo	GSK3196165 180mg	Total
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Total of all reporting groups
Overall Participants	22	22	44
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (6.80)	60.9 (6.25)	58.8 (6.79)
Sex: Female, Male (Count of Participants)
Female	20 90.9%	20 90.9%	40 90.9%
Male	2 9.1%	2 9.1%	4 9.1%
Race/Ethnicity, Customized (Number) [Number]
White - White /Caucasian/European	22 100%	22 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6
Description	Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo).
Time Frame	Baseline (Day 1 Pre-dose) and Week 6

Outcome Measure Data

Analysis Population Description

Intent To Treat Population. Only non-missing data is included MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	21	20
Least Squares Mean (Standard Error) [Scores on scale]	-1.34 (0.325)	-1.70 (0.334)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.442
	Comments	MMRM model with fixed effects of Baseline Value,Treatment Group,Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used.p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -1.31 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 6 is presented.

2. Secondary Outcome

Title	Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Description	Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score is calculated by sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

Outcome Measure Data

Analysis Population Description

Intent To Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1, n=22, 20	-0.13 (0.152)	-0.59 (0.160)
Week 2, n=21, 20	-0.48 (0.230)	-0.86 (0.239)
Week 3, n=21, 20	-0.74 (0.279)	-1.24 (0.289)
Week 4, n=21, 20	-0.91 (0.291)	-1.65 (0.301)
Week 6, n=21, 20	-1.34 (0.325)	-1.70 (0.334)
Week 8, n=20, 19	-1.27 (0.382)	-2.10 (0.393)
Week 10, n=20, 19	-1.18 (0.376)	-2.09 (0.389)
Week 12, n=19, 18	-1.35 (0.402)	-2.24 (0.416)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.90 to -0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 1 is presented

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.257
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -1.05 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 2 is presented

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.220
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -1.31 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 3 is presented

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -1.59 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 4 is presented

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.442
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -1.31 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 6 is presented

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.139
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -1.93 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 8 is presented

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.103
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95%; -2.00 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 10 is presented

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.132
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.06 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 12 is presented.

3. Secondary Outcome

Title	Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Description	Participants were required to complete a daily pain NRS based on their 24-hour worst hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The score is calculated as sum of daily 24 hours worst hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1, n=22, 20	0.01 (0.174)	-0.45 (0.183)
Week 2, n=21, 20	-0.42 (0.235)	-0.69 (0.245)
Week 3, n=21, 20	-0.63 (0.269)	-1.23 (0.278)
Week 4, n= 21, 20	-0.72 (0.289)	-1.51 (0.299)
Week 6, n= 21, 20	-1.30 (0.328)	-1.63 (0.337)
Week 8, n= 20, 19	-1.18 (0.394)	-2.11 (0.406)
Week 10, n= 20, 19	-1.15 (0.394)	-2.13 (0.407)
Week 12, n= 19, 18	-1.32 (0.415)	-2.34 (0.430)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.082
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.97 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 1 is presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.426
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.96 to 0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 2 is presented

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.129
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -1.38 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 3 is presented

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.067
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.63 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 4 is presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.494
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -1.28 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 6 is presented

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.94
	Confidence Interval	(2-Sided) 95%; -2.08 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 8 is presented.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -2.13 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 10 is presented.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -2.22 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 12 is presented.

4. Secondary Outcome

Title	Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Description	Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 30 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is reported.
Time Frame	Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1	0 0%	9 40.9%
Week 2	0 0%	18 81.8%
Week 3	5 22.7%	23 104.5%
Week 4	14 63.6%	41 186.4%
Week 6	23 104.5%	45 204.5%
Week 8	18 81.8%	50 227.3%
Week 10	18 81.8%	50 227.3%
Week 12	23 104.5%	45 204.5%
Follow up (Week 22)	23 104.5%	27 122.7%

5. Secondary Outcome

Title	Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Description	Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 50 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
Time Frame	Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1	0 0%	0 0%
Week 2	0 0%	9 40.9%
Week 3	0 0%	18 81.8%
Week 4	0 0%	23 104.5%
Week 6	14 63.6%	27 122.7%
Week 8	14 63.6%	41 186.4%
Week 10	9 40.9%	36 163.6%
Week 12	14 63.6%	41 186.4%
Follow up (Week 22)	9 40.9%	23 104.5%

6. Secondary Outcome

Title	Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Description	Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 30 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
Time Frame	Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1	0 0%	9 40.9%
Week 2	0 0%	18 81.8%
Week 3	0 0%	23 104.5%
Week 4	0 0%	32 145.5%
Week 6	9 40.9%	36 163.6%
Week 8	9 40.9%	45 204.5%
Week 10	14 63.6%	45 204.5%
Week 12	14 63.6%	45 204.5%
Follow up (Week 22)	14 63.6%	32 145.5%

7. Secondary Outcome

Title	Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Description	Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 50 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
Time Frame	Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1	0 0%	0 0%
Week 2	0 0%	5 22.7%
Week 3	0 0%	14 63.6%
Week 4	0 0%	18 81.8%
Week 6	5 22.7%	18 81.8%
Week 8	5 22.7%	32 145.5%
Week 10	5 22.7%	27 122.7%
Week 12	9 40.9%	36 163.6%
Follow up (Week 22)	5 22.7%	23 104.5%

8. Secondary Outcome

Title	Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Description	The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours. All items are rated on NRS scale with anchors "0" (none) to "10" (extreme). The scores for the pain and physical function components were calculated as simple summation of the item scores relating to that domain, so the Pain component ranges from 0 (i.e. all pain item scores are scored 0 [none]) to 50 (i.e. all pain item scores are scored 10 [extreme]), and the Physical Function component ranges from 0 (i.e. all physical function item scores are scored 0 [none]) to 90 (i.e. all physical function item scores are scored 10 [extreme]). The total AUSCAN score was calculated as simple summation of the 15 item scores and therefore ranges from 0 to 150. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Pain, Week 1, n=22, 20	0.8 (0.98)	-1.9 (1.03)
Pain, Week 2, n=21, 21	-1.8 (1.27)	-3.7 (1.28)
Pain, Week 4, n=22, 21	-3.5 (1.61)	-7.2 (1.64)
Pain, Week 6, n=22, 21	-6.6 (1.72)	-7.6 (1.76)
Pain, Week 8, n=20, 20	-4.9 (1.93)	-8.7 (1.97)
Pain, Week 10, n=20, 20	-5.3 (1.82)	-10.9 (1.87)
Pain, Week 12, n=21, 19	-4.6 (1.84)	-9.3 (1.91)
Stiffness, Week 1, n= 22, 20	-0.4 (0.29)	-0.6 (0.31)
Stiffness, Week 2, n= 21, 21	-0.8 (0.33)	-1.1 (0.33)
Stiffness, Week 4, n= 22, 21	-1.2 (0.41)	-1.8 (0.42)
Stiffness, Week 6, n= 22, 21	-1.4 (0.39)	-1.6 (0.40)
Stiffness, Week 8, n= 20, 20	-1.2 (0.41)	-1.9 (0.42)
Stiffness, Week 10, n= 20, 20	-1.6 (0.44)	-2.2 (0.45)
Stiffness, Week 12, n= 21, 19	-1.5 (0.45)	-2.2 (0.47)
Physical function, Week 1, n=22, 20	-0.7 (2.08)	-3.6 (2.16)
Physical function, Week 2, n=21,21	-2.8 (2.35)	-5.7 (2.37)
Physical function, Week 4, n=22, 21	-6.4 (3.01)	-11.3 (3.07)
Physical function, Week 6, n=22, 21	-9.1 (3.25)	-11.8 (3.32)
Physical function, Week 8, n=20, 20	-8.3 (3.57)	-13.2 (3.64)
Physical function, Week 10, n=20, 20	-9.0 (3.82)	-15.2 (3.92)
Physical function, Week 12, n=21, 19	-7.2 (3.74)	-15.4 (3.87)
Total, Week 1, n= 22, 20	-0.5 (3.07)	-6.0 (3.20)
Total, Week 2, n= 21, 21	-5.7 (3.66)	-10.4 (3.70)
Total, Week 4, n= 22, 21	-11.4 (4.72)	-20.1 (4.83)
Total, Week 6, n= 22, 21	-17.3 (5.17)	-20.7 (5.28)
Total, Week 8, n= 20, 20	-14.6 (5.70)	-23.6 (5.81)
Total, Week 10, n= 20, 20	-16.1 (5.88)	-28.2 (6.04)
Total, Week 12, n= 21, 19	-13.5 (5.92)	-26.7 (6.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -5.6 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component, Week 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.282
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -5.6 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component, Week 2

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.113
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -8.4 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component Week 4

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.695
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -5.9 to 4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component, Week 6

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.176
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -9.4 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component, Week 8

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 95%; -10.8 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component, Week 10

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.082
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -10.1 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Pain component, Week 12

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.587
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 1

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.457
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 2

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.298
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.8 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 4

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.726
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 6

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.213
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 8

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.331
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 10

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.248
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.1 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Stiffness component, Week 12

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.350
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -9.0 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 1

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.383
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -9.8 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 2

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.271
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -13.5 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 4

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.565
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -12.1 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 6

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -15.2 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 8

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.266
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -17.3 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 10

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.136
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.2
	Confidence Interval	(2-Sided) 95%; -19.1 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Physical Function component, Week 12

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.230
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 95%; -14.5 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 1

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.381
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -15.2 to 5.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 2

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.207
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.7
	Confidence Interval	(2-Sided) 95%; -22.4 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 4

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.648
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -18.4 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 6

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-9.0
	Confidence Interval	(2-Sided) 95%; -25.4 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 8

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.1
	Confidence Interval	(2-Sided) 95%; -29.1 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 10

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.127
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-13.3
	Confidence Interval	(2-Sided) 95%; -30.5 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	For Total of all component scores, Week 12

9. Secondary Outcome

Title	Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Description	Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1, n = 22, 21	-0.3 (0.64)	-0.3 (0.66)
Week 2, n = 21, 21	-1.6 (0.85)	-1.2 (0.86)
Week 4, n = 22, 21	-1.6 (0.76)	-2.1 (0.78)
Week 6, n = 22, 21	-3.7 (0.83)	-2.3 (0.85)
Week 8, n = 20, 20	-3.0 (0.92)	-2.8 (0.94)
Week 10, n = 20, 20	-2.6 (1.08)	-2.9 (1.10)
Week 12, n = 21, 19	-2.9 (0.91)	-3.1 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.957
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 1 is presented

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.775
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -2.1 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 2 is presented

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.624
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -2.7 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 4 is presented

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.243
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 6 is presented

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.875
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -2.5 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 8 is presented

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.848
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -3.4 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 10 is presented

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.883
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -2.8 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 12 is presented

10. Secondary Outcome

Title	Change From Baseline in Number of Tender Hand Joints at Each Visit
Description	Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored >0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data was included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 1, n= 22, 21	-0.6 (1.10)	-1.8 (1.13)
Week 2, n= 21, 21	-1.7 (1.15)	-2.1 (1.17)
Week 4, n= 22, 21	-1.1 (1.33)	-3.0 (1.36)
Week 6, n= 22, 21	-3.7 (1.27)	-4.2 (1.30)
Week 8, n= 20, 20	-2.4 (1.36)	-3.9 (1.39)
Week 10, n= 20, 20	-3.7 (1.45)	-4.4 (1.48)
Week 12, n= 21, 19	-3.5 (1.46)	-4.0 (1.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.463
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -4.4 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 1 is presented

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -3.7 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 2 is presented

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.324
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -5.8 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 4 is presented

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.783
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -4.2 to 3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 6 is presented

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.464
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -5.4 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 8 is presented

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.736
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -4.9 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 10 is presented

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.806
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -4.8 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 12 is presented

11. Secondary Outcome

Title	Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Description	Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 2, n= 19, 14	-1.8 (0.39)	-1.5 (0.45)
Week 4, n= 20, 15	-2.1 (0.44)	-2.6 (0.50)
Week 8, n= 17, 15	-2.2 (0.52)	-3.4 (0.57)
Week 12, n= 18, 14	-2.7 (0.56)	-3.0 (0.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.586
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 2 is presented

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.416
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 4 is presented

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.120
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.8 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 8 is presented

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.687
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -2.1 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 12 is presented

12. Secondary Outcome

Title	Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Description	Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time Frame	Baseline, Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Week 2, n= 20, 21	-0.4 (0.36)	-0.6 (0.35)
Week 4, n= 21, 21	-0.6 (0.42)	-1.3 (0.42)
Week 8, n= 19, 20	-0.9 (0.47)	-1.8 (0.46)
Week 12, n= 20, 19	-0.7 (0.46)	-1.8 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.651
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 2 is presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.271
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 4 is presented

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.186
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -2.2 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 8 is presented

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK3196165 180mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments	MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
	Method	Mixed Model Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference from placebo for Week 12 is presented

13. Secondary Outcome

Title	Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who received at least one dose of study treatment (GSK3196165 or placebo) were included in Safety Population.
Time Frame	Up to Week 22

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Any AE	11 50%	13 59.1%
Any SAE	1 4.5%	2 9.1%

14. Secondary Outcome

Title	Number of Participants With Infections
Description	Adverse events of special interest (AESI) included serious infections like serious respiratory infections and tuberculosis and other opportunistic infections. Number of participants with infections has been reported.
Time Frame	Up to Week 22

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Serious Infections	0 0%	0 0%
Opportunistic Infections	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With Pulmonary Events
Description	Pulmonary events like pulmonary alveolar proteinosis (PAP), persistent (for 3 consecutive weeks) reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) > 15 percentage, persistent (for 3 consecutive weeks) cough and/or dyspnea and non- life threatening pulmonary changes related to surfactant accumulation is presented.
Time Frame	Up to Week 22

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Persistent dyspnea	0 0%	0 0%
Persistent decrease in DLCO	0 0%	0 0%
Persistent Cough	0 0%	0 0%
Abnormal Lung Auscultation	0 0%	0 0%
PAP	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With Anti-GSK3196165 Binding Antibodies
Description	Serum samples were collected at indicated time points for anti-drug antibody (ADA) measurements. Anti-GSK3196165 binding antibody detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. The number of participants with change from Baseline to any time post Baseline in the results of immunogenicity assessment as indicated by: negative to positive, positive to positive, positive to negative and negative to negative are presented.
Time Frame	Up to Week 22

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants with data available post-Baseline are reported.

Arm/Group Title	Placebo	GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22	22
Negative to positive	0 0%	1 4.5%
Positive to positive	0 0%	0 0%
Positive to negative	0 0%	0 0%
Negative to negative	22 100%	20 90.9%

17. Secondary Outcome

Title	Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165
Description	Blood samples were collected at indicated time points and CL/F was estimated using population PK analysis. Participants in the 'Safety' population who have at least one valid PK assessment were included Pharmacokinetic (PK) Population.
Time Frame	Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	GSK3196165 180mg
Arm/Group Description	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	21
Geometric Mean (Geometric Coefficient of Variation) [Liters per day]	4.94 (68.8)

18. Secondary Outcome

Title	Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165
Description	Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis.
Time Frame	Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Outcome Measure Data

Analysis Population Description

PK Population.

Arm/Group Title	GSK3196165 180mg
Arm/Group Description	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	21
Geometric Mean (Geometric Coefficient of Variation) [Liters]	36.5 (61.5)

19. Secondary Outcome

Title	Absoption Rate Constant (Ka) of GSK3196165
Description	Blood samples were collected at indicated time points and Ka was estimated using population PK analysis.
Time Frame	Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	GSK3196165 180mg
Arm/Group Description	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	21
Geometric Mean (Geometric Coefficient of Variation) [Per day]	0.205 (72.3)

20. Secondary Outcome

Title	Serum Concentration of GSK3196165 by Visit
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis.
Time Frame	Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

Arm/Group Title	GSK3196165 180 mg
Arm/Group Description	Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Measure Participants	22
Day 3, n= 18	2457.05 (94.74)
Week 1, n= 21	1767.55 (46.96)
Week 4, n= 21	2821.12 (61.00)
Week 6, n= 20	1802.09 (60.42)
Week 12, n= 8	800.96 (176.33)
Follow up (Week 22), n= 12	56.40 (346.41)

Adverse Events

Time Frame	Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Adverse Event Reporting Description	Non-serious AEs and SAE for Safety Population was reported.
Arm/Group Title	Placebo		GSK3196165 180mg
Arm/Group Description	Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).		Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
All Cause Mortality
	Placebo		GSK3196165 180mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Placebo		GSK3196165 180mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		2/22 (9.1%)
Cardiac disorders
ATRIAL FIBRILLATION	1/22 (4.5%)	1	0/22 (0%)	0
Injury, poisoning and procedural complications
HUMERUS FRACTURE	0/22 (0%)	0	1/22 (4.5%)	1
Vascular disorders
HYPERTENSIVE CRISIS	0/22 (0%)	0	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Placebo		GSK3196165 180mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/22 (18.2%)		10/22 (45.5%)
Cardiac disorders
PALPITATIONS	2/22 (9.1%)	2	0/22 (0%)	0
General disorders
INJECTION SITE ERYTHEMA	0/22 (0%)	0	2/22 (9.1%)	3
INJECTION SITE RASH	0/22 (0%)	0	2/22 (9.1%)	6
Infections and infestations
CONJUNCTIVITIS	0/22 (0%)	0	2/22 (9.1%)	2
HERPES ZOSTER	0/22 (0%)	0	2/22 (9.1%)	2
NASOPHARYNGITIS	1/22 (4.5%)	1	2/22 (9.1%)	3
URINARY TRACT INFECTION	0/22 (0%)	0	2/22 (9.1%)	2
Respiratory, thoracic and mediastinal disorders
COUGH	2/22 (9.1%)	3	2/22 (9.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.