Trial Outcomes & Findings for Evaluation of Pharmacokinetics and Safety of GSK3196165 in Combination With Methotrexate in Japanese Subjects With Rheumatoid Arthritis (NCT NCT03028467)

Last Updated: 2019-06-26

Results Overview

Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by non-compartmental analysis using the concentration data after last dosing (Day 71). Only those participants whose parameters could be determined were analyzed. PK Population included all GSK3196165-treated participants from whom PK samples were collected and analyzed.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155

Results posted on

2019-06-26

Participant Flow

This study was conducted to assess pharmacokinetics (PK), safety, tolerability and efficacy of GSK3196165 for 12 weeks, in combination with Methotrexate (MTX), in Japanese participants with active moderate-severe rheumatoid arthritis (RA) despite treatment with MTX. Participants were enrolled at 15 centers in Japan from 24-Jan-2017 to 30-Jun-2017.

A total of 35 participants were screened, and 20 participants failed screening because of not met eligibility criteria (18 participants) and withdrawal by participant (2 participants). Hence, a total of 15 participants were enrolled and randomized to study treatment.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo weekly as a single subcutaneous (SC) injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then every other week (EOW) injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 45 mg Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Overall Study STARTED	4	3	4	4
Overall Study COMPLETED	4	3	4	4
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Pharmacokinetics and Safety of GSK3196165 in Combination With Methotrexate in Japanese Subjects With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=4 Participants Participants received placebo weekly as a single subcutaneous (SC) injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then every other week (EOW) injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 45 mg n=3 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=4 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	Total n=15 Participants Total of all reporting groups
Age, Continuous	52.0 Years STANDARD_DEVIATION 14.45 • n=5 Participants	58.0 Years STANDARD_DEVIATION 15.72 • n=7 Participants	66.5 Years STANDARD_DEVIATION 2.52 • n=5 Participants	52.0 Years STANDARD_DEVIATION 9.20 • n=4 Participants	57.1 Years STANDARD_DEVIATION 11.82 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Race/Ethnicity, Customized Race · Japanese/East Asian Heritage (EAH)/South EAH	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants

PRIMARY outcome

Timeframe: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=2 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Maximum Observed Concentration (Cmax) of GSK3196165	699.92 Nanogram per milliliter (ng/mL) Interval 48.18 to 10167.77	1444.88 Nanogram per milliliter (ng/mL) Interval 148.02 to 14104.11	3924.10 Nanogram per milliliter (ng/mL) Interval 3375.18 to 4562.3	—

PRIMARY outcome

Timeframe: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155

Population: PK Population. Only those participants whose parameters could be determined were analyzed (represented by n=X in the category titles).

Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by non-compartmental analysis using the concentration data after last dosing (Day 71). NA indicates data was not available as geometric mean and/or 95 percent confidence interval could not be calculated when number of participant was not sufficient.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=3 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=4 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]), AUC From Time Zero Extrapolated to Infinity (AUC [0-inf]), AUC Over the Dosing Interval (AUCtau) of GSK3196165 AUC (0-t), n=2, 3, 4	189948.606 HourNanogram per milliliter (hrng/mL) Interval 508.091 to 71011815.71	386497.495 HourNanogram per milliliter (hrng/mL) Interval 32248.035 to 4632229.918	1186604.746 HourNanogram per milliliter (hrng/mL) Interval 589936.272 to 2386750.721	—
Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]), AUC From Time Zero Extrapolated to Infinity (AUC [0-inf]), AUC Over the Dosing Interval (AUCtau) of GSK3196165 AUC (0-inf), n=0, 1, 2	—	732243.847 HourNanogram per milliliter (hrng/mL) NA indicates data was not available as 95 percent confidence interval could not be calculated when number of participant was not sufficient.	1097422.958 HourNanogram per milliliter (hrng/mL) Interval 106189.728 to 11341371.436	—
Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]), AUC From Time Zero Extrapolated to Infinity (AUC [0-inf]), AUC Over the Dosing Interval (AUCtau) of GSK3196165 AUCtau, n=1, 3, 4	196562.287 HourNanogram per milliliter (hrng/mL) NA indicates data was not available as 95 percent confidence interval could not be calculated when number of participant was not sufficient.	303167.467 HourNanogram per milliliter (hrng/mL) Interval 38999.824 to 2356690.471	787570.414 HourNanogram per milliliter (hrng/mL) Interval 570081.863 to 1088031.733	—

PRIMARY outcome

Timeframe: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155

Population: PK Population. Only those participants whose parameters could be determined were analyzed.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=2 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Time to Reach Cmax (Tmax) of GSK3196165	48.99167 Hour Interval 46.35 to 51.6333	70.61667 Hour Interval 47.25 to 94.0667	69.80000 Hour Interval 47.4 to 70.8	—

PRIMARY outcome

Timeframe: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155.

Population: PK Population. Only those participants whose parameters could be determined were analyzed.

Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by standard non-compartmental analysis from the concentration data after last dosing (Day 71). NA indicates data was not available as 95 percent confidence interval could not be calculated when number of participant was not sufficient.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=1 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=2 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Terminal Half-life (t1/2) of GSK3196165	—	282.85265 Hour NA indicates data was not available as 95 percent confidence interval could not be calculated when number of participant was not sufficient.	245.12966 Hour Interval 66.51778 to 903.3457	—

PRIMARY outcome

Timeframe: Up to 22 weeks

Population: Intent-to-Treat (ITT) Population. It included all participants who were randomized to treatment and who received at least one dose of study treatment.

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 that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. AESI included serious infections including serious respiratory infections and tuberculosis and opportunistic infections, neutropenia (grade 3 or 4), respiratory events, pulmonary alveolar proteinosis, hypersensitivity reactions including anaphylaxis and injection site reactions.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Number of Participants With Any Adverse Event (AE), Serious AE (SAE) and Adverse Events of Special Interest (AESI) Any AE	3 Participants	2 Participants	3 Participants	2 Participants
Number of Participants With Any Adverse Event (AE), Serious AE (SAE) and Adverse Events of Special Interest (AESI) Any SAE	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Adverse Event (AE), Serious AE (SAE) and Adverse Events of Special Interest (AESI) Any AESI	2 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and up to 22 weeks

Population: ITT Population

Vital sign measurements including SBP and DBP were measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to 22 weeks

Population: ITT Population

Vital sign measurements including HR was measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Change From Baseline in Heart Rate (HR) Week 1	0.3 Beats per minute Standard Deviation 5.12	-8.0 Beats per minute Standard Deviation 3.61	11.5 Beats per minute Standard Deviation 13.30	-0.8 Beats per minute Standard Deviation 4.27
Change From Baseline in Heart Rate (HR) Week 2	3.0 Beats per minute Standard Deviation 11.34	-5.3 Beats per minute Standard Deviation 2.31	9.5 Beats per minute Standard Deviation 15.15	-5.0 Beats per minute Standard Deviation 1.41
Change From Baseline in Heart Rate (HR) Week 3	1.3 Beats per minute Standard Deviation 3.59	-5.3 Beats per minute Standard Deviation 3.79	10.8 Beats per minute Standard Deviation 18.10	-7.0 Beats per minute Standard Deviation 5.94
Change From Baseline in Heart Rate (HR) Week 4	2.5 Beats per minute Standard Deviation 5.45	-5.7 Beats per minute Standard Deviation 14.01	12.0 Beats per minute Standard Deviation 15.12	-7.8 Beats per minute Standard Deviation 2.06
Change From Baseline in Heart Rate (HR) Week 6	7.3 Beats per minute Standard Deviation 10.11	-7.3 Beats per minute Standard Deviation 6.43	11.0 Beats per minute Standard Deviation 15.92	-0.5 Beats per minute Standard Deviation 11.50
Change From Baseline in Heart Rate (HR) Week 8	5.8 Beats per minute Standard Deviation 8.26	-2.7 Beats per minute Standard Deviation 10.12	1.8 Beats per minute Standard Deviation 11.30	-11.5 Beats per minute Standard Deviation 6.66
Change From Baseline in Heart Rate (HR) Week 10	8.3 Beats per minute Standard Deviation 9.07	1.3 Beats per minute Standard Deviation 8.02	0.8 Beats per minute Standard Deviation 11.41	-8.8 Beats per minute Standard Deviation 10.94
Change From Baseline in Heart Rate (HR) Week 12	-2.0 Beats per minute Standard Deviation 8.68	-10.0 Beats per minute Standard Deviation 7.00	12.5 Beats per minute Standard Deviation 11.03	-7.8 Beats per minute Standard Deviation 5.56
Change From Baseline in Heart Rate (HR) Follow up (Week 22)	-2.3 Beats per minute Standard Deviation 7.14	-6.0 Beats per minute Standard Deviation 11.53	6.3 Beats per minute Standard Deviation 20.34	-1.3 Beats per minute Standard Deviation 8.22

SECONDARY outcome

Timeframe: Baseline and up to 22 weeks

Population: ITT Population

Vital sign measurements including body temperature was measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Change From Baseline in Body Temperature Week 1	0.00 Celsius Standard Deviation 0.469	-0.20 Celsius Standard Deviation 0.346	0.18 Celsius Standard Deviation 0.287	0.05 Celsius Standard Deviation 0.265
Change From Baseline in Body Temperature Week 2	0.07 Celsius Standard Deviation 0.330	0.03 Celsius Standard Deviation 0.153	-0.13 Celsius Standard Deviation 0.250	0.22 Celsius Standard Deviation 0.718
Change From Baseline in Body Temperature Week 3	-0.10 Celsius Standard Deviation 0.476	-0.30 Celsius Standard Deviation 0.265	0.18 Celsius Standard Deviation 0.359	0.15 Celsius Standard Deviation 0.843
Change From Baseline in Body Temperature Week 4	-0.20 Celsius Standard Deviation 0.327	-0.47 Celsius Standard Deviation 0.379	0.20 Celsius Standard Deviation 0.316	-0.15 Celsius Standard Deviation 0.387
Change From Baseline in Body Temperature Week 6	-0.03 Celsius Standard Deviation 0.377	0.07 Celsius Standard Deviation 0.404	-0.10 Celsius Standard Deviation 0.200	-0.02 Celsius Standard Deviation 0.457
Change From Baseline in Body Temperature Week 8	-0.20 Celsius Standard Deviation 0.424	0.03 Celsius Standard Deviation 0.503	-0.07 Celsius Standard Deviation 0.377	0.05 Celsius Standard Deviation 0.332
Change From Baseline in Body Temperature Week 10	0.00 Celsius Standard Deviation 0.337	0.13 Celsius Standard Deviation 0.252	-0.02 Celsius Standard Deviation 0.386	0.17 Celsius Standard Deviation 0.499
Change From Baseline in Body Temperature Week 12	-0.07 Celsius Standard Deviation 0.427	0.00 Celsius Standard Deviation 0.458	-0.25 Celsius Standard Deviation 0.370	0.02 Celsius Standard Deviation 0.670
Change From Baseline in Body Temperature Follow up (Week 22)	-0.47 Celsius Standard Deviation 0.862	-0.13 Celsius Standard Deviation 0.208	0.25 Celsius Standard Deviation 0.311	-0.18 Celsius Standard Deviation 0.171

SECONDARY outcome

Timeframe: Baseline and up to 22 weeks

Population: ITT Population

Vital sign measurements including respiratory rate was measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Change From Baseline in Respiratory Rate Week 1	-2.0 Breaths per minute Standard Deviation 1.63	0.7 Breaths per minute Standard Deviation 1.15	-1.0 Breaths per minute Standard Deviation 1.41	0.8 Breaths per minute Standard Deviation 2.22
Change From Baseline in Respiratory Rate Week 2	-0.5 Breaths per minute Standard Deviation 3.42	0.0 Breaths per minute Standard Deviation 0.00	-1.0 Breaths per minute Standard Deviation 2.00	0.3 Breaths per minute Standard Deviation 1.26
Change From Baseline in Respiratory Rate Week 3	0.3 Breaths per minute Standard Deviation 3.10	1.3 Breaths per minute Standard Deviation 2.31	0.8 Breaths per minute Standard Deviation 0.96	1.5 Breaths per minute Standard Deviation 3.11
Change From Baseline in Respiratory Rate Week 4	-2.5 Breaths per minute Standard Deviation 3.42	-1.7 Breaths per minute Standard Deviation 2.89	-0.5 Breaths per minute Standard Deviation 2.38	0.3 Breaths per minute Standard Deviation 1.71
Change From Baseline in Respiratory Rate Week 6	1.5 Breaths per minute Standard Deviation 5.45	-1.0 Breaths per minute Standard Deviation 1.73	-0.3 Breaths per minute Standard Deviation 0.96	2.3 Breaths per minute Standard Deviation 5.19
Change From Baseline in Respiratory Rate Week 8	-0.3 Breaths per minute Standard Deviation 2.63	1.3 Breaths per minute Standard Deviation 2.31	-1.3 Breaths per minute Standard Deviation 0.96	0.3 Breaths per minute Standard Deviation 1.71
Change From Baseline in Respiratory Rate Week 10	0.0 Breaths per minute Standard Deviation 1.63	-0.7 Breaths per minute Standard Deviation 1.15	-2.3 Breaths per minute Standard Deviation 1.50	1.0 Breaths per minute Standard Deviation 3.46
Change From Baseline in Respiratory Rate Week 12	1.0 Breaths per minute Standard Deviation 1.41	-0.3 Breaths per minute Standard Deviation 2.52	-2.5 Breaths per minute Standard Deviation 3.11	0.8 Breaths per minute Standard Deviation 3.59
Change From Baseline in Respiratory Rate Follow up (Week 22)	0.0 Breaths per minute Standard Deviation 0.82	0.3 Breaths per minute Standard Deviation 3.51	-1.5 Breaths per minute Standard Deviation 2.08	0.5 Breaths per minute Standard Deviation 1.00

SECONDARY outcome

Timeframe: At Week 12

Population: ITT Population

12-Lead ECGs were taken using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) intervals. Number of participants with any abnormal findings in ECG recordings were summarized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings Abnormal - Not clinically significant	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings Abnormal - Clinically significant	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 22 weeks

Population: ITT Population

Blood samples were collected to evaluate hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), erythrocytes, reticulocytes, white blood cells (WBC), total neutrophils, eosinophils, basophils, monocytes, lymphocytes, platelet count, activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, erythrocyte sedimentation rate (ESR). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose lab value category was unchanged (e.g. High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if they had values that changed 'To Low' and 'To High', so the percentages may not add to 100% in such instances.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Number of Participants With Emergent Hematology Results Relative to Normal Range Basophils, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCH, To Normal or No change	3 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Total neutrophils, To High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Platelet count, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range WBC, To Normal or No change	4 Participants	3 Participants	4 Participants	3 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range APTT, To Low	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range APTT, To Normal or No change	3 Participants	3 Participants	3 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range APTT, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Basophils, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Basophils, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Eosinophils, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Eosinophils, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Eosinophils, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range ESR, To low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Hemoglobin, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range ESR, To Normal or No change	2 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range ESR, To High	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Fibrinogen, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Fibrinogen, To Normal or No change	3 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Fibrinogen, To High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Hemoglobin, To Low	1 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Hemoglobin, To Normal or No change	3 Participants	2 Participants	2 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Hematocrit, To Low	1 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Hematocrit, To Normal or No change	3 Participants	1 Participants	3 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Hematocrit, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Lymphocytes, To Low	2 Participants	1 Participants	3 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Lymphocytes, To Normal or No change	2 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Lymphocytes, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCHC, To Low	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCHC, To Normal or No change	3 Participants	2 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCHC, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCH, To Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCH, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCV, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCV, To Normal or No change	3 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range MCV, To High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Monocytes, To Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Monocytes, To Normal or No change	2 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Monocytes, To High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Total neutrophils, To Low	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Total neutrophils, To Normal or No change	4 Participants	2 Participants	3 Participants	3 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Platelet count, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Platelet count, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range PT, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range PT, To Normal or No change	4 Participants	2 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range PT, To High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range RBC, To Low	0 Participants	0 Participants	3 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range RBC, To Normal or No change	4 Participants	3 Participants	1 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range RBC, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Reticulocytes, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Reticulocytes, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range Reticulocytes, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range WBC, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Hematology Results Relative to Normal Range WBC, To High	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 22 weeks

Population: ITT Population

Blood samples were collected to evaluate Albumin, Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Total Bilirubin, Calcium, Cholesterol, Creatine Kinase, C-Reactive protein (CRP), Creatinine, Gamma Glutamyl Transferase (GGT), Glucose, High Density Lipids (HDL), Potassium, Lactate Dehydrogenase, Low Density Lipids (LDL), Sodium, Phosphorus inorganic, Triglycerides, Total Protein and Urea. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose lab value category was unchanged (e.g. High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if they had values that changed 'To Low' and 'To High', so the percentages may not add to 100% in such instances.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Albumin, To Normal or No change	4 Participants	3 Participants	2 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Albumin, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range ALP, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range ALT, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range ALT, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range AST, To Normal or No change	4 Participants	3 Participants	4 Participants	3 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Total Bilirubin, To Low	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Total Bilirubin, To Normal or No change	2 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Total Bilirubin, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Calcium, To Low	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Calcium, To Normal or No change	3 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Calcium, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Cholesterol, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Cholesterol, To Normal or No change	2 Participants	2 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Cholesterol, To High	2 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Creatine Kinase, To Low	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Creatine Kinase, To Normal or No change	3 Participants	2 Participants	4 Participants	3 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Creatine Kinase, To High	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range CRP, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range CRP, To Normal or No change	2 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Creatinine, To Low	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Creatinine, To Normal or No change	4 Participants	2 Participants	3 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range GGT, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range GGT, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range GGT, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Glucose, To Low	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Glucose, To Normal or No change	1 Participants	2 Participants	3 Participants	2 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Glucose, To High	3 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range HDL, To Normal or No change	4 Participants	2 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range HDL, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Potassium To Low	2 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Potassium, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Lactate Dehydrogenase, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Lactate Dehydrogenase, To Normal or No change	3 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Lactate Dehydrogenase, To High	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range LDL, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range LDL, To Normal or No change	2 Participants	2 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range LDL, To High	2 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Sodium, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Sodium, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Sodium, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Phosphorus inorganic, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Phosphorus inorganic, To Normal or No change	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Triglycerides, To Low	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Triglycerides, To Normal or No change	4 Participants	3 Participants	4 Participants	3 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Triglycerides, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Total Protein, To Normal or No change	3 Participants	2 Participants	3 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Urea, To Normal or No change	3 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Urea, To High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Albumin, To Low	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range ALP, To Normal or No change	2 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range ALP, To High	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range ALT, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range AST, To Low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range AST, To High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range CRP, To High	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Creatinine, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range HDL, To Low	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Potassium, To Normal or No change	2 Participants	2 Participants	3 Participants	4 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Phosphorus inorganic, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Total Protein, To Low	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Total Protein, To High	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range Urea, To Low	1 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 22 weeks

Population: ITT Population

Urine samples were collected for analysis of presence of glucose and protein in urine by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine protein and glucose can be read as negative, Trace, 1+, 2+ and 3+, indicating proportional concentrations in the urine sample

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Number of Participants With Urinalysis Dipstick Findings Week 4, Protein, 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Protein, Negative	1 Participants	3 Participants	2 Participants	4 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Glucose, 1+	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Glucose, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Glucose, 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Glucose, Negative	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Protein, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Protein, Trace	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Glucose, 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Glucose, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Glucose, Negative	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Glucose, Trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Protein, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Protein, Negative	2 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Protein, Trace	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Glucose, 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Glucose, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Glucose, 3+	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Glucose, Negative	4 Participants	3 Participants	4 Participants	3 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Glucose, Trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Protein, 1+	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Protein, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 4, Protein, Trace	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Glucose, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Glucose, 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Glucose, Negative	4 Participants	3 Participants	4 Participants	3 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Glucose, Trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Protein, 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Protein, 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Protein, 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Protein, Negative	1 Participants	3 Participants	3 Participants	2 Participants
Number of Participants With Urinalysis Dipstick Findings Week 8, Protein, Trace	3 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Glucose, 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Glucose, Trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Protein, 1+	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Protein, 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Week 12, Protein, Negative	3 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Glucose, 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Protein, 1+	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Urinalysis Dipstick Findings Follow up (Week 22), Protein, 3+	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 2, 4, 12 and 22

Population: Immunogenicity Population. The immunogenicity Population included all participants in the ITT Population, who had at least one immunogenicity assessment.

Serum samples were collected and tested for presence of antibodies that bind to GSK3196165. The presence of treatment emergent anti-drug antibodies (ADA) were determined using a GSK3196165 bridging style ADA assay with a bio-analytically determined cut point determined during assay validation. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Baseline was considered as the latest pre-dose assessment. Number of participants with post-Baseline negative or positive anti-GSK3196165 antibody test results were presented.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 2, Positive	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 2, Negative	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 4, Negative	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 12, Positive	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 12, Negative	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 22 (Follow up), Positive	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 22 (Follow up), Negative	4 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Anti-GSK3196165 Antibody Test Results Week 4, Positive	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, up to Week 22

Population: ITT Population

DAS28 (CRP) is a measure of disease activity in rheumatoid arthritis obtained by examination of 28 joints for swelling and tenderness using CRP as a blood biomarker for inflammation. Its components include: Tender/Painful Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), CRP and Patient's Global Assessment of Arthritis. DAS28 (CRP) was calculated by 0.56 (square root of TJC28)+ 0.28 (square root of SJC28)+ 0.36 (natural logarithm \[CRP+1\])+ (0.014\*patients global assessment)+0.96. Scores ranges from 0 to infinity, where higher scores indicates high disease activity. Scores higher than 5.1 indicates high disease activity and scores lower than 2.6 indicates remission. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value. Adjusted mean and standard error of adjusted mean are presented using Mixed Model for Repeated Measures.

Outcome measures

Outcome measures
Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 1	-0.2179 Scores on a scale Standard Error 0.44925	-1.3289 Scores on a scale Standard Error 0.51977	-0.7356 Scores on a scale Standard Error 0.42589	-0.7511 Scores on a scale Standard Error 0.42569
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 2	0.1643 Scores on a scale Standard Error 0.48797	-0.9744 Scores on a scale Standard Error 0.56457	-0.7262 Scores on a scale Standard Error 0.46260	-0.6404 Scores on a scale Standard Error 0.46238
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 4	-0.0887 Scores on a scale Standard Error 0.59912	-1.5462 Scores on a scale Standard Error 0.69316	-0.9781 Scores on a scale Standard Error 0.56796	-1.2502 Scores on a scale Standard Error 0.56769
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 6	-0.5455 Scores on a scale Standard Error 0.55367	-0.8664 Scores on a scale Standard Error 0.64058	-0.7330 Scores on a scale Standard Error 0.52487	-1.0048 Scores on a scale Standard Error 0.52463
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 8	-0.2710 Scores on a scale Standard Error 0.69364	-0.9231 Scores on a scale Standard Error 0.80253	-0.8209 Scores on a scale Standard Error 0.65757	-1.2375 Scores on a scale Standard Error 0.65726
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 12	-0.8234 Scores on a scale Standard Error 0.76338	-1.1810 Scores on a scale Standard Error 0.88321	-0.6383 Scores on a scale Standard Error 0.72368	-0.9415 Scores on a scale Standard Error 0.72335
Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints Week 22 (Follow-up)	-0.3044 Scores on a scale Standard Error 0.62302	-1.7320 Scores on a scale Standard Error 0.72082	0.2371 Scores on a scale Standard Error 0.59062	-1.0976 Scores on a scale Standard Error 0.59035

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

GSK3196165 45 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

GSK3196165 90 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GSK3196165 180 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=4 participants at risk Participants received placebo weekly as a single subcutaneous (SC) injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then every other week (EOW) injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 45 mg n=3 participants at risk Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=4 participants at risk Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 participants at risk Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Pleurisy	25.0% 1/4 • Serious adverse events (SAEs) and non-serious adverse events (non-serious AEs) were collected from the start of the study treatment up to Week 22. SAEs and non-serious AEs were reported for the ITT Population.	0.00% 0/3 • Serious adverse events (SAEs) and non-serious adverse events (non-serious AEs) were collected from the start of the study treatment up to Week 22. SAEs and non-serious AEs were reported for the ITT Population.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious adverse events (non-serious AEs) were collected from the start of the study treatment up to Week 22. SAEs and non-serious AEs were reported for the ITT Population.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious adverse events (non-serious AEs) were collected from the start of the study treatment up to Week 22. SAEs and non-serious AEs were reported for the ITT Population.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	GSK3196165 45 mg n=4 Participants Participants received GSK3196165 45 milligram (mg) weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 90 mg n=3 Participants Participants received GSK3196165 90 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.	GSK3196165 180 mg n=4 Participants Participants received GSK3196165 180 mg weekly as a single SC injection by an un-blinded administrator. There were 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants also received a stable dose of MTX during the Treatment Period.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 1	-0.3 Millimeter of mercury Standard Deviation 8.62	-7.7 Millimeter of mercury Standard Deviation 2.89	-15.0 Millimeter of mercury Standard Deviation 17.36	-1.0 Millimeter of mercury Standard Deviation 8.45
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 2	-1.8 Millimeter of mercury Standard Deviation 8.34	-6.7 Millimeter of mercury Standard Deviation 12.06	-4.5 Millimeter of mercury Standard Deviation 12.48	1.5 Millimeter of mercury Standard Deviation 1.91
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 3	0.5 Millimeter of mercury Standard Deviation 4.80	-1.7 Millimeter of mercury Standard Deviation 12.01	-10.5 Millimeter of mercury Standard Deviation 20.47	-0.8 Millimeter of mercury Standard Deviation 6.02
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 4	-5.8 Millimeter of mercury Standard Deviation 10.14	-11.3 Millimeter of mercury Standard Deviation 17.10	-3.3 Millimeter of mercury Standard Deviation 17.88	6.3 Millimeter of mercury Standard Deviation 7.63
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 6	-2.0 Millimeter of mercury Standard Deviation 5.66	-12.7 Millimeter of mercury Standard Deviation 11.59	-1.3 Millimeter of mercury Standard Deviation 15.50	-2.3 Millimeter of mercury Standard Deviation 11.62
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 8	-6.3 Millimeter of mercury Standard Deviation 7.41	-3.0 Millimeter of mercury Standard Deviation 13.00	-5.8 Millimeter of mercury Standard Deviation 18.55	3.8 Millimeter of mercury Standard Deviation 2.22
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 10	2.3 Millimeter of mercury Standard Deviation 4.86	6.7 Millimeter of mercury Standard Deviation 5.03	-11.8 Millimeter of mercury Standard Deviation 23.04	-1.5 Millimeter of mercury Standard Deviation 2.65
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 12	2.0 Millimeter of mercury Standard Deviation 11.49	-5.3 Millimeter of mercury Standard Deviation 9.45	-2.5 Millimeter of mercury Standard Deviation 14.29	0.8 Millimeter of mercury Standard Deviation 6.60
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Follow up (Week 22)	4.0 Millimeter of mercury Standard Deviation 13.88	-4.7 Millimeter of mercury Standard Deviation 14.50	-2.5 Millimeter of mercury Standard Deviation 22.52	-4.3 Millimeter of mercury Standard Deviation 3.50
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 1	-1.0 Millimeter of mercury Standard Deviation 4.08	-3.3 Millimeter of mercury Standard Deviation 10.97	-6.8 Millimeter of mercury Standard Deviation 6.85	-0.5 Millimeter of mercury Standard Deviation 8.35
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 2	-1.5 Millimeter of mercury Standard Deviation 7.33	0.3 Millimeter of mercury Standard Deviation 1.53	2.0 Millimeter of mercury Standard Deviation 5.60	-0.3 Millimeter of mercury Standard Deviation 5.44
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 3	-4.3 Millimeter of mercury Standard Deviation 6.95	-1.0 Millimeter of mercury Standard Deviation 6.56	-5.3 Millimeter of mercury Standard Deviation 9.57	-4.3 Millimeter of mercury Standard Deviation 2.75
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 4	-1.0 Millimeter of mercury Standard Deviation 7.39	-1.3 Millimeter of mercury Standard Deviation 3.79	1.3 Millimeter of mercury Standard Deviation 7.46	1.3 Millimeter of mercury Standard Deviation 6.60
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 6	-1.0 Millimeter of mercury Standard Deviation 8.04	7.7 Millimeter of mercury Standard Deviation 5.77	5.3 Millimeter of mercury Standard Deviation 11.03	-5.5 Millimeter of mercury Standard Deviation 4.12
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 8	-2.5 Millimeter of mercury Standard Deviation 3.32	11.3 Millimeter of mercury Standard Deviation 7.02	-1.5 Millimeter of mercury Standard Deviation 10.66	-2.0 Millimeter of mercury Standard Deviation 10.39
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 10	-2.3 Millimeter of mercury Standard Deviation 3.59	2.7 Millimeter of mercury Standard Deviation 10.26	-3.0 Millimeter of mercury Standard Deviation 8.83	-4.5 Millimeter of mercury Standard Deviation 3.70
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 12	3.5 Millimeter of mercury Standard Deviation 6.24	-1.7 Millimeter of mercury Standard Deviation 4.73	-3.8 Millimeter of mercury Standard Deviation 10.53	-4.3 Millimeter of mercury Standard Deviation 6.40
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Follow up (Week 22)	2.8 Millimeter of mercury Standard Deviation 6.99	-1.0 Millimeter of mercury Standard Deviation 8.72	3.0 Millimeter of mercury Standard Deviation 12.54	-3.5 Millimeter of mercury Standard Deviation 5.26