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Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (contRAst 1)

Primary Purpose

Arthritis, Rheumatoid

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

GSK3196165 (Otilimab)

Tofacitinib 5 mg

Placebo

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Rheumatoid arthritis, GSK3196165, Otilimab, Tofacitinib, Methotrexate, Placebo

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key inclusion criteria

>=18 years of age
Has had RA for >=6 months and was not diagnosed before 16 years of age
Has active disease, as defined by having both:*
- >=6/68 tender/painful joint count (TJC), and
- >=6/66 swollen joint count (SJC)
Has at least 1 bone erosion present on hand/wrist or foot radiographs
Has had an inadequate response to MTX, despite currently taking MTX 15-25 mg/week** oral or injected
- If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC.
  - A lower dose of 7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX or per local requirement.

Key exclusion criteria

Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections.
Has received prior treatment with an antagonist of GM-CSF or its receptor or Janus kinase (JAK) inhibitors (either experimental or approved)
Has received prior treatment with a biologic Disease-modifying antirheumatic drug (DMARD) which has been discontinued due to an inadequate response.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

GSK3196165 90mg + MTX

GSK3196165 150mg + MTX

Tofacitinib 5mg + MTX

Placebo + MTX and GSK3196165 90mg + MTX

Placebo + MTX and GSK3196165 150mg + MTX

Placebo + MTX and Tofacitinib 5mg + MTX

Arm Description

Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with MTX.

Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with MTX plus placebo injection weekly to maintain the blind for 52 weeks.

Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with MTX until Week 52.

Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with MTX until Week 52.

Participants received Placebo capsule weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with MTX plus placebo injection to maintain the blind for 52 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving 20 Percentage (%) Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo

ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) [visual analogue scale (VAS) with values from 0=best to 100=worst], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Secondary Outcome Measures

Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score Less Than or Equal to (<=)10 [CDAI Low Disease Activity (LDA)] at Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms.

Percentage of Participants Achieving 20% Improvement in ACR20 at Week 24 (Non-Inferiority Versus Tofacitinib)

Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 24 and ACR 20/50/70 at and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein mg/L (hsCRP)].

Percentage of Participants Achieving ACR20/50/70 at Week 24 and Week 52 for Placebo Switched Arms

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Placebo Switched Arms

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8.

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Placebo Switched Arms

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8.

Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 12

ACR50/70 is calculated as a 50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Placebo Switched Arms

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Placebo Switched Arms

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for Placebo Switched Arms

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for Placebo Switched Arms

Percentage of Participants Achieving a Good/Moderate (European League Against Rheumatism) EULAR Response at Week 12

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response at given time point was defined based on the combination of current DAS28 score and improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response), (>0.6 to <=1.2:moderate response) and (<=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response), (>0.6 to <=1.2:moderate response) and (<=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response), (>0.6 to <=1.2:no response) and (<=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

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

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Placebo Switched Arms

Number of Participants Achieving ACR/EULAR Remission at Week 12

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Placebo Switched Arms

Percentage of Participants Achieving no Radiographic Progression (Van Der Heijde Modified Total Sharp Scores (mTSS <= 0.5) at Week 12

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Percentage of Participants Achieving no Radiographic Progression (mTSS <= 0.5) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Percentage of Participants Achieving no Radiographic Progression (mTSS <= 0.5) at Week 24 and Week 52 for Placebo Switched Arms

Change From Baseline in CDAI Total Score at Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (PtGA and PhGA VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

CDAI total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Placebo Switched Arms

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 12

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Placebo Switched Arms

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Change From Baseline in Van Der Heijde mTSS at Week 12

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Van Der Heijde mTSS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Van Der Heijde mTSS at Week 24 and Week 52 for Placebo Switched Arms

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Placebo Switched Arms

Change From Baseline in Arthritis Pain VAS at Week 12

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Placebo Switched Arms

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Change From Baseline in Short Form (SF)-36 Physical Component Scores (PCS) at Week 12

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits.CB=subtracting PD visit value from BV.For purpose of all analyses up to week12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms.

Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits.CB=subtracting PD visit value from BV.For purpose of all analyses up to week12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms.

Change From Baseline in SF-36 Domain Scores at Week 12

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (SF, vitality, MH, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP and GH).The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring of SF-36.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits. CB=subtracting PD visit value from BV. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Change From Baseline in SF-36 Domain Scores at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Placebo Switched Arms

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains (PF,role-physical,BP,GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Placebo Switched Arms

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Change From Baseline in SF-36 Domain Scores at Week 24 and Week 52 for Placebo Switched Arms

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning(PF), bodily pain(BP), role limitations due to physical and emotional problems, general health(GH), mental health(MH), social functioning(SF), vitality. The MCS consists of 4 domains (SF, vitality, MH, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP, GH). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Placebo Switched Arms

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)

An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) for Placebo Switched Arms

Change From Baseline in White Blood Cell (WBC) Count at Week 12

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in WBC Count at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in WBC Count at Week 24 and Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 12

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Hematology Parameter of Hemoglobin at Week 12

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 and Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma-Glutamyl Transpeptidase (GGT) at Week 12

Blood samples were collected for the assessment of clinical chemistry parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT) levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Clinical Chemistry Parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Clinical Chemistry Parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for Placebo Switched Arms

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 12

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 12

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 12

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Placebo Switched Arms

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Lipid Profile Parameter of Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein-cholesterol at Week 12

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Placebo Switched Arms

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Placebo Switched Arms

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 12

Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Placebo Switched Arms

Blood samples were collected for the assessment of fasting lipid profile including triglycerides. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Placebo Switched Arms

Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities

Number of participants with NCI-CTCAE >=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case >=Grade 3 shifts from Baseline. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.

Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities for Placebo Switched Arms

Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody

Concentrations of GM-CSF autoantibodies were determined.

Number of Participants With Anti-GSK3196165 Antibodies

Serum samples were collected for the determination of anti- GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA.

Full Information

NCT ID

NCT03980483

First Posted

May 15, 2019

Last Updated

September 29, 2023

Sponsor

GlaxoSmithKline

Collaborators

Iqvia Pty Ltd

1. Study Identification

Unique Protocol Identification Number

NCT03980483

Brief Title

Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Acronym

contRAst 1

Official Title

A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study Comparing GSK3196165 With Placebo and With Tofacitinib, in Combination With Methotrexate in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

May 16, 2019 (Actual)

Primary Completion Date

September 15, 2021 (Actual)

Study Completion Date

August 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

Collaborators

Iqvia Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study [contRAst 1 (201790: NCT03980483)] is a phase 3, randomized, multicenter, double blind study to assess the safety and efficacy of GSK3196165, in combination with methotrexate (MTX), for the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to MTX. The study will consist of a screening phase of up to 6 weeks followed by a 52-week treatment phase in which participants will be randomized in a ratio of 6:6:3:1:1:1 to receive GSK3196165 150 milligrams (mg) subcutaneous (SC) weekly, GSK3196165 90 mg SC weekly, tofacitinib capsules (cap) 5 mg twice a day or placebo (three arms, each placebo arm will have 12 weeks placebo followed by 40 weeks active treatment) respectively, all in combination with MTX. Participants who, in investigator's judgement will benefit from extended treatment with GSK3196165, may be included in the long-term extension study [contRAst X (209564: NCT04333147)]. For those participants who do not continue into the long term-extension study, there will be an 8 week safety follow-up visit following the treatment phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

Keywords

Rheumatoid arthritis, GSK3196165, Otilimab, Tofacitinib, Methotrexate, Placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Participants will be randomized to one of six intervention arms in ratio of 6:6:3:1:1:1.

Masking

ParticipantInvestigator

Masking Description

Double blinded

Allocation

Randomized

Enrollment

1537 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GSK3196165 90mg + MTX

Arm Type

Experimental

Arm Description

Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

Arm Title

GSK3196165 150mg + MTX

Arm Type

Experimental

Arm Description

Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with MTX.

Arm Title

Tofacitinib 5mg + MTX

Arm Type

Active Comparator

Arm Description

Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with MTX plus placebo injection weekly to maintain the blind for 52 weeks.

Arm Title

Placebo + MTX and GSK3196165 90mg + MTX

Arm Type

Placebo Comparator

Arm Description

Arm Title

Placebo + MTX and GSK3196165 150mg + MTX

Arm Type

Placebo Comparator

Arm Description

Arm Title

Placebo + MTX and Tofacitinib 5mg + MTX

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

GSK3196165 (Otilimab)

Intervention Description

GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

Intervention Type

Drug

Intervention Name(s)

Tofacitinib 5 mg

Intervention Description

Tofacitinib cap (over encapsulated 5mg tablet) to be administered orally.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/pre-filled syringe (PFS) to be administered SC.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo cap (containing lactose) to be administered orally.

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving 20 Percentage (%) Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo

Description

Time Frame

Week 12

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score Less Than or Equal to (<=)10 [CDAI Low Disease Activity (LDA)] at Week 12

Description

Time Frame

Week 12

Title

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Percentage of Participants Achieving 20% Improvement in ACR20 at Week 24 (Non-Inferiority Versus Tofacitinib)

Description

Time Frame

Week 24

Title

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving ACR20/50/70 at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 12

Description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time Frame

Week 12

Title

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8.

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Placebo Switched Arms

Description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8.

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants Achieving Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants Achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Placebo Switched Arms

Description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12

Description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time Frame

Week 12

Title

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving a Good/Moderate (European League Against Rheumatism) EULAR Response at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Number of Participants Achieving ACR/EULAR Remission at Week 12

Description

Time Frame

Week 12

Title

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving no Radiographic Progression (Van Der Heijde Modified Total Sharp Scores (mTSS <= 0.5) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants Achieving no Radiographic Progression (mTSS <= 0.5) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Week 24 and Week 52

Title

Percentage of Participants Achieving no Radiographic Progression (mTSS <= 0.5) at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Week 24 and Week 52

Title

Change From Baseline in CDAI Total Score at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Placebo Switched Arms

Description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Van Der Heijde mTSS at Week 12

Description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Van Der Heijde mTSS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Van Der Heijde mTSS at Week 24 and Week 52 for Placebo Switched Arms

Description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Arthritis Pain VAS at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Placebo Switched Arms

Description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Short Form (SF)-36 Physical Component Scores (PCS) at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in SF-36 Domain Scores at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in SF-36 Domain Scores at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Placebo Switched Arms

Description

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains (PF,role-physical,BP,GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Placebo Switched Arms

Description

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in SF-36 Domain Scores at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Placebo Switched Arms

Description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)

Description

Time Frame

Up to Week 59

Title

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) for Placebo Switched Arms

Description

Time Frame

Up to Week 59

Title

Change From Baseline in White Blood Cell (WBC) Count at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in WBC Count at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in WBC Count at Week 24 and Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Week 12), Week 24 and Week 52

Title

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Week 12), Week 24 and Week 52

Title

Change From Baseline in Hematology Parameter of Hemoglobin at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 and Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Week 12), Week 24 and Week 52

Title

Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma-Glutamyl Transpeptidase (GGT) at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Clinical Chemistry Parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Clinical Chemistry Parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for Placebo Switched Arms

Description

Time Frame

Baseline (Week 12), Week 24 and Week 52

Title

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Week 12), Week 24 and Week 52

Title

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1), Week 24 and Week 52

Title

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Week 12), Week 24 and Week 52

Title

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1) and Week 24

Title

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Day 1) and Week 24

Title

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1) and Week 52

Title

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Day 1) and Week 52

Title

Change From Baseline in Lipid Profile Parameter of Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein-cholesterol at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1) and Week 24

Title

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Day 1) and Week 24

Title

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1) and Week 52

Title

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Placebo Switched Arms

Description

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Time Frame

Baseline (Day 1) and Week 52

Title

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 12

Description

Time Frame

Baseline (Day 1) and Week 12

Title

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1) and Week 24

Title

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Placebo Switched Arms

Description

Time Frame

Baseline (Day 1) and Week 24

Title

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Description

Time Frame

Baseline (Day 1) and Week 52

Title

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Placebo Switched Arms

Description

Time Frame

Baseline (Day 1) and Week 52

Title

Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities

Description

Time Frame

Up to Week 59

Title

Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities for Placebo Switched Arms

Description

Time Frame

Up to Week 59

Title

Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody

Description

Concentrations of GM-CSF autoantibodies were determined.

Time Frame

At baseline

Title

Number of Participants With Anti-GSK3196165 Antibodies

Description

Time Frame

Up to Week 59

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key inclusion criteria >=18 years of age Has had RA for >=6 months and was not diagnosed before 16 years of age Has active disease, as defined by having both:* >=6/68 tender/painful joint count (TJC), and >=6/66 swollen joint count (SJC) Has at least 1 bone erosion present on hand/wrist or foot radiographs Has had an inadequate response to MTX, despite currently taking MTX 15-25 mg/week** oral or injected If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC. A lower dose of 7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX or per local requirement. Key exclusion criteria Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections. Has received prior treatment with an antagonist of GM-CSF or its receptor or Janus kinase (JAK) inhibitors (either experimental or approved) Has received prior treatment with a biologic Disease-modifying antirheumatic drug (DMARD) which has been discontinued due to an inadequate response.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36207

Country

United States

Facility Name

GSK Investigational Site

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85032

Country

United States

Facility Name

GSK Investigational Site

City

Sun City

State/Province

Arizona

ZIP/Postal Code

85351

Country

United States

Facility Name

GSK Investigational Site

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85704

Country

United States

Facility Name

GSK Investigational Site

City

Covina

State/Province

California

ZIP/Postal Code

91722

Country

United States

Facility Name

GSK Investigational Site

City

San Diego

State/Province

California

ZIP/Postal Code

92128

Country

United States

Facility Name

GSK Investigational Site

City

Upland

State/Province

California

ZIP/Postal Code

91786

Country

United States

Facility Name

GSK Investigational Site

City

Whittier

State/Province

California

ZIP/Postal Code

90602

Country

United States

Facility Name

GSK Investigational Site

City

Brandon

State/Province

Florida

ZIP/Postal Code

33511

Country

United States

Facility Name

GSK Investigational Site

City

Daytona Beach

State/Province

Florida

ZIP/Postal Code

32117

Country

United States

Facility Name

GSK Investigational Site

City

DeBary

State/Province

Florida

ZIP/Postal Code

32713

Country

United States

Facility Name

GSK Investigational Site

City

Fort Lauderdale

State/Province

Florida

ZIP/Postal Code

33309

Country

United States

Facility Name

GSK Investigational Site

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33016

Country

United States

Facility Name

GSK Investigational Site

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32207

Country

United States

Facility Name

GSK Investigational Site

City

Miami Lakes

State/Province

Florida

ZIP/Postal Code

33014

Country

United States

Facility Name

GSK Investigational Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33155

Country

United States

Facility Name

GSK Investigational Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33165

Country

United States

Facility Name

GSK Investigational Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33173

Country

United States

Facility Name

GSK Investigational Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

GSK Investigational Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33614

Country

United States

Facility Name

GSK Investigational Site

City

Newnan

State/Province

Georgia

ZIP/Postal Code

30265

Country

United States

Facility Name

GSK Investigational Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60607

Country

United States

Facility Name

GSK Investigational Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60640

Country

United States

Facility Name

GSK Investigational Site

City

Wheaton

State/Province

Maryland

ZIP/Postal Code

20902

Country

United States

Facility Name

GSK Investigational Site

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

GSK Investigational Site

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68516

Country

United States

Facility Name

GSK Investigational Site

City

Minot

State/Province

North Dakota

ZIP/Postal Code

58701

Country

United States

Facility Name

GSK Investigational Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45242

Country

United States

Facility Name

GSK Investigational Site

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45417

Country

United States

Facility Name

GSK Investigational Site

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

GSK Investigational Site

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29601

Country

United States

Facility Name

GSK Investigational Site

City

Baytown

State/Province

Texas

ZIP/Postal Code

77521

Country

United States

Facility Name

GSK Investigational Site

City

College Station

State/Province

Texas

ZIP/Postal Code

77845

Country

United States

Facility Name

GSK Investigational Site

City

Colleyville

State/Province

Texas

ZIP/Postal Code

76034

Country

United States

Facility Name

GSK Investigational Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77089

Country

United States

Facility Name

GSK Investigational Site

City

Lubbock

State/Province

Texas

ZIP/Postal Code

79410

Country

United States

Facility Name

GSK Investigational Site

City

San Marcos

State/Province

Texas

ZIP/Postal Code

78666

Country

United States

Facility Name

GSK Investigational Site

City

The Woodlands

State/Province

Texas

ZIP/Postal Code

77382

Country

United States

Facility Name

GSK Investigational Site

City

Waco

State/Province

Texas

ZIP/Postal Code

76710

Country

United States

Facility Name

GSK Investigational Site

City

Ciudad Autonoma Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

C1417

Country

Argentina

Facility Name

GSK Investigational Site

City

Ciudad Autonoma Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

C1430EGF

Country

Argentina

Facility Name

GSK Investigational Site

City

Ciudad Autonoma de Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

1426

Country

Argentina

Facility Name

GSK Investigational Site

City

Ciudad Autonoma de Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

C1046AAQ

Country

Argentina

Facility Name

GSK Investigational Site

City

Ciudad Autonoma de Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

C1431FWO

Country

Argentina

Facility Name

GSK Investigational Site

City

La Palta

State/Province

Buenos Aires

ZIP/Postal Code

B1900AXI

Country

Argentina

Facility Name

GSK Investigational Site

City

Mar del Plata

State/Province

Buenos Aires

ZIP/Postal Code

B7600FYK

Country

Argentina

Facility Name

GSK Investigational Site

City

San Isidro

State/Province

Buenos Aires

ZIP/Postal Code

1643

Country

Argentina

Facility Name

GSK Investigational Site

City

San Nicolas

State/Province

Buenos Aires

ZIP/Postal Code

B2900DMH

Country

Argentina

Facility Name

GSK Investigational Site

City

Córdoba

State/Province

Córdova

ZIP/Postal Code

X5000AVE

Country

Argentina

Facility Name

GSK Investigational Site

City

Rosario

State/Province

Santa Fe

ZIP/Postal Code

S2000DSV

Country

Argentina

Facility Name

GSK Investigational Site

City

Buenos Aires

ZIP/Postal Code

C1430CKE

Country

Argentina

Facility Name

GSK Investigational Site

City

Ciudad Autónoma de Buenos Aires

ZIP/Postal Code

C1426BOR

Country

Argentina

Facility Name

GSK Investigational Site

City

Salta

ZIP/Postal Code

A4400ANW

Country

Argentina

Facility Name

GSK Investigational Site

City

San Juan

ZIP/Postal Code

J5402DIL

Country

Argentina

Facility Name

GSK Investigational Site

City

Santiago Del Estero

ZIP/Postal Code

G4200DYB

Country

Argentina

Facility Name

GSK Investigational Site

City

Brampton

State/Province

Ontario

ZIP/Postal Code

L6T 0G1

Country

Canada

Facility Name

GSK Investigational Site

City

Trois-Rivieres

State/Province

Quebec

ZIP/Postal Code

G8Z 1Y2

Country

Canada

Facility Name

GSK Investigational Site

City

Bengbu

State/Province

Anhui

ZIP/Postal Code

233004

Country

China

Facility Name

GSK Investigational Site

City

Pingxiang

State/Province

Jiangxi

ZIP/Postal Code

337055

Country

China

Facility Name

GSK Investigational Site

City

Changchun

State/Province

Jilin

ZIP/Postal Code

130021

Country

China

Facility Name

GSK Investigational Site

City

Chengdu

State/Province

Sichuan

ZIP/Postal Code

610041

Country

China

Facility Name

GSK Investigational Site

City

Shanghai

ZIP/Postal Code

200052

Country

China

Facility Name

GSK Investigational Site

City

Brno

ZIP/Postal Code

638 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Brno

ZIP/Postal Code

65691

Country

Czechia

Facility Name

GSK Investigational Site

City

Ostrava

ZIP/Postal Code

70200

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 10

ZIP/Postal Code

10000

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 2

ZIP/Postal Code

128 50

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 4 Nusle

ZIP/Postal Code

140 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 4

ZIP/Postal Code

140 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 4

ZIP/Postal Code

148 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 5

ZIP/Postal Code

150 06

Country

Czechia

Facility Name

GSK Investigational Site

City

Uherske Hradiste

ZIP/Postal Code

686 01

Country

Czechia

Facility Name

GSK Investigational Site

City

Zlin

ZIP/Postal Code

760 01

Country

Czechia

Facility Name

GSK Investigational Site

City

Baja

ZIP/Postal Code

6500

Country

Hungary

Facility Name

GSK Investigational Site

City

Balatonfured

ZIP/Postal Code

8230

Country

Hungary

Facility Name

GSK Investigational Site

City

Budapest

ZIP/Postal Code

1023

Country

Hungary

Facility Name

GSK Investigational Site

City

Budapest

ZIP/Postal Code

1033

Country

Hungary

Facility Name

GSK Investigational Site

City

Budapest

ZIP/Postal Code

1036

Country

Hungary

Facility Name

GSK Investigational Site

City

Kistarcsa

ZIP/Postal Code

2143

Country

Hungary

Facility Name

GSK Investigational Site

City

Szekesfehervar

ZIP/Postal Code

8000

Country

Hungary

Facility Name

GSK Investigational Site

City

Szentes

ZIP/Postal Code

6600

Country

Hungary

Facility Name

GSK Investigational Site

City

Székesfehérvár

ZIP/Postal Code

8000

Country

Hungary

Facility Name

GSK Investigational Site

City

Veszprem

ZIP/Postal Code

H-8200

Country

Hungary

Facility Name

GSK Investigational Site

City

Ahmedabad

ZIP/Postal Code

380005

Country

India

Facility Name

GSK Investigational Site

City

Ahmedabad

ZIP/Postal Code

380013

Country

India

Facility Name

GSK Investigational Site

City

Ahmedabad

ZIP/Postal Code

380016

Country

India

Facility Name

GSK Investigational Site

City

Ahmedabad

ZIP/Postal Code

380054

Country

India

Facility Name

GSK Investigational Site

City

Banglore

ZIP/Postal Code

560070

Country

India

Facility Name

GSK Investigational Site

City

Belagavi

ZIP/Postal Code

590010

Country

India

Facility Name

GSK Investigational Site

City

Hubli

ZIP/Postal Code

580021

Country

India

Facility Name

GSK Investigational Site

City

Hyderabad

ZIP/Postal Code

500018

Country

India

Facility Name

GSK Investigational Site

City

Jaipur

ZIP/Postal Code

302001

Country

India

Facility Name

GSK Investigational Site

City

Jaipur

ZIP/Postal Code

302006

Country

India

Facility Name

GSK Investigational Site

City

Kolkata

ZIP/Postal Code

700020

Country

India

Facility Name

GSK Investigational Site

City

Nagpur

ZIP/Postal Code

440009

Country

India

Facility Name

GSK Investigational Site

City

Nagpur

ZIP/Postal Code

440012

Country

India

Facility Name

GSK Investigational Site

City

Nashik

ZIP/Postal Code

422005

Country

India

Facility Name

GSK Investigational Site

City

Nashik

ZIP/Postal Code

422101

Country

India

Facility Name

GSK Investigational Site

City

New Delhi

ZIP/Postal Code

110060

Country

India

Facility Name

GSK Investigational Site

City

Pimpri-Chinchwad

ZIP/Postal Code

411033

Country

India

Facility Name

GSK Investigational Site

City

Pune

ZIP/Postal Code

411004

Country

India

Facility Name

GSK Investigational Site

City

Pune

ZIP/Postal Code

411057

Country

India

Facility Name

GSK Investigational Site

City

Rajkot

ZIP/Postal Code

360005

Country

India

Facility Name

GSK Investigational Site

City

Surat

ZIP/Postal Code

395002

Country

India

Facility Name

GSK Investigational Site

City

Vadodara

ZIP/Postal Code

390001

Country

India

Facility Name

GSK Investigational Site

City

Verona

State/Province

Veneto

ZIP/Postal Code

37126

Country

Italy

Facility Name

GSK Investigational Site

City

Adazi

ZIP/Postal Code

LV2164

Country

Latvia

Facility Name

GSK Investigational Site

City

Liepaja

ZIP/Postal Code

LV-3401

Country

Latvia

Facility Name

GSK Investigational Site

City

Riga

ZIP/Postal Code

LV 1038

Country

Latvia

Facility Name

GSK Investigational Site

City

Kaunas

ZIP/Postal Code

LT-45130

Country

Lithuania

Facility Name

GSK Investigational Site

City

Kaunas

ZIP/Postal Code

LT-50128

Country

Lithuania

Facility Name

GSK Investigational Site

City

Klaipeda

ZIP/Postal Code

LT-92288

Country

Lithuania

Facility Name

GSK Investigational Site

City

Siauliai

ZIP/Postal Code

76231

Country

Lithuania

Facility Name

GSK Investigational Site

City

Vilnius

ZIP/Postal Code

LT-01117

Country

Lithuania

Facility Name

GSK Investigational Site

City

Klang

ZIP/Postal Code

41200

Country

Malaysia

Facility Name

GSK Investigational Site

City

Kuala Lumpur

ZIP/Postal Code

59100

Country

Malaysia

Facility Name

GSK Investigational Site

City

Seremban, Negeri Sembilan

ZIP/Postal Code

70300

Country

Malaysia

Facility Name

GSK Investigational Site

City

Sibu

ZIP/Postal Code

96000

Country

Malaysia

Facility Name

GSK Investigational Site

City

Mexicali

State/Province

Baja California Sur

ZIP/Postal Code

21100

Country

Mexico

Facility Name

GSK Investigational Site

City

Leon

State/Province

Guanajuato

ZIP/Postal Code

37000

Country

Mexico

Facility Name

GSK Investigational Site

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44130

Country

Mexico

Facility Name

GSK Investigational Site

City

Morelia

State/Province

Michoacán

ZIP/Postal Code

58000

Country

Mexico

Facility Name

GSK Investigational Site

City

Durango

ZIP/Postal Code

34270

Country

Mexico

Facility Name

GSK Investigational Site

City

Mexico

ZIP/Postal Code

6700

Country

Mexico

Facility Name

GSK Investigational Site

City

Bialystok

ZIP/Postal Code

15-351

Country

Poland

Facility Name

GSK Investigational Site

City

Bydgoszcz

ZIP/Postal Code

85-168

Country

Poland

Facility Name

GSK Investigational Site

City

Czestochowa

ZIP/Postal Code

42202

Country

Poland

Facility Name

GSK Investigational Site

City

Gdansk

ZIP/Postal Code

80-382

Country

Poland

Facility Name

GSK Investigational Site

City

Gdynia

ZIP/Postal Code

81-338

Country

Poland

Facility Name

GSK Investigational Site

City

Gdynia

ZIP/Postal Code

81-537

Country

Poland

Facility Name

GSK Investigational Site

City

Katowice

ZIP/Postal Code

40-040

Country

Poland

Facility Name

GSK Investigational Site

City

Katowice

ZIP/Postal Code

40-282

Country

Poland

Facility Name

GSK Investigational Site

City

Kraków

ZIP/Postal Code

30-363

Country

Poland

Facility Name

GSK Investigational Site

City

Lodz

ZIP/Postal Code

90-127

Country

Poland

Facility Name

GSK Investigational Site

City

Lublin

ZIP/Postal Code

20-362

Country

Poland

Facility Name

GSK Investigational Site

City

Lublin

ZIP/Postal Code

20-582

Country

Poland

Facility Name

GSK Investigational Site

City

Nowa Sol

ZIP/Postal Code

67-100

Country

Poland

Facility Name

GSK Investigational Site

City

Olsztyn

ZIP/Postal Code

10-117

Country

Poland

Facility Name

GSK Investigational Site

City

Poznan

ZIP/Postal Code

60-529

Country

Poland

Facility Name

GSK Investigational Site

City

Poznan

ZIP/Postal Code

60-702

Country

Poland

Facility Name

GSK Investigational Site

City

Poznan

ZIP/Postal Code

60-773

Country

Poland

Facility Name

GSK Investigational Site

City

Sochaczew

ZIP/Postal Code

96-500

Country

Poland

Facility Name

GSK Investigational Site

City

Staszow

ZIP/Postal Code

28-200

Country

Poland

Facility Name

GSK Investigational Site

City

Torun

ZIP/Postal Code

87-100

Country

Poland

Facility Name

GSK Investigational Site

City

Warsaw

ZIP/Postal Code

02-673

Country

Poland

Facility Name

GSK Investigational Site

City

Warszawa

ZIP/Postal Code

00-465

Country

Poland

Facility Name

GSK Investigational Site

City

Warszawa

ZIP/Postal Code

00-874

Country

Poland

Facility Name

GSK Investigational Site

City

Warszawa

ZIP/Postal Code

01-192

Country

Poland

Facility Name

GSK Investigational Site

City

Warszawa

ZIP/Postal Code

02-118

Country

Poland

Facility Name

GSK Investigational Site

City

Wrocław

ZIP/Postal Code

50-381

Country

Poland

Facility Name

GSK Investigational Site

City

Zamosc

ZIP/Postal Code

22-400

Country

Poland

Facility Name

GSK Investigational Site

City

Ekaterinburg

ZIP/Postal Code

620043

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Kemerovo

ZIP/Postal Code

650066

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Korolev

ZIP/Postal Code

141060

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Krasnoyarsk

ZIP/Postal Code

660062

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Moscow

ZIP/Postal Code

111539

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Moscow

ZIP/Postal Code

115404

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Moscow

ZIP/Postal Code

115522

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Novosibirsk

ZIP/Postal Code

630091

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Omsk

ZIP/Postal Code

644024

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Saint Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Saint-Petersburg

ZIP/Postal Code

190068

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Saratov

ZIP/Postal Code

410054

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Smolensk

ZIP/Postal Code

214025

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Tomsk

ZIP/Postal Code

634050

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Tver

ZIP/Postal Code

170036

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Ulyanovsk

ZIP/Postal Code

432063

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Yaroslavl

ZIP/Postal Code

150003

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Yaroslavl

ZIP/Postal Code

150007

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Yaroslavl

ZIP/Postal Code

150062

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Belgrade

ZIP/Postal Code

11000

Country

Serbia

Facility Name

GSK Investigational Site

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

2113

Country

South Africa

Facility Name

GSK Investigational Site

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0122

Country

South Africa

Facility Name

GSK Investigational Site

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

184

Country

South Africa

Facility Name

GSK Investigational Site

City

Umhlanga

State/Province

KwaZulu- Natal

ZIP/Postal Code

4319

Country

South Africa

Facility Name

GSK Investigational Site

City

Bellville

ZIP/Postal Code

7530

Country

South Africa

Facility Name

GSK Investigational Site

City

Bloemfontein

ZIP/Postal Code

9301

Country

South Africa

Facility Name

GSK Investigational Site

City

Cape Town

ZIP/Postal Code

7405

Country

South Africa

Facility Name

GSK Investigational Site

City

Johannesburg

ZIP/Postal Code

2193

Country

South Africa

Facility Name

GSK Investigational Site

City

Kempton Park

ZIP/Postal Code

1619

Country

South Africa

Facility Name

GSK Investigational Site

City

Panorama, Cape Town

ZIP/Postal Code

7500

Country

South Africa

Facility Name

GSK Investigational Site

City

Pretoria

ZIP/Postal Code

0002

Country

South Africa

Facility Name

GSK Investigational Site

City

Somerset West

ZIP/Postal Code

7130

Country

South Africa

Facility Name

GSK Investigational Site

City

Stellenbosch

ZIP/Postal Code

7600

Country

South Africa

Facility Name

GSK Investigational Site

City

A Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

GSK Investigational Site

City

Cordoba

ZIP/Postal Code

140044

Country

Spain

Facility Name

GSK Investigational Site

City

Santiago de Compostela

ZIP/Postal Code

15706

Country

Spain

Facility Name

GSK Investigational Site

City

Cherkasy

ZIP/Postal Code

18009

Country

Ukraine

Facility Name

GSK Investigational Site

City

Ivano-Frankivsk

ZIP/Postal Code

76018

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kharkiv

ZIP/Postal Code

61039

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kharkiv

ZIP/Postal Code

61124

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kharkiv

ZIP/Postal Code

61176

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

02091

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

03037

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

03680

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

04054

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

1023

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

2002

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

2125

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kyiv

ZIP/Postal Code

3049

Country

Ukraine

Facility Name

GSK Investigational Site

City

Lutsk

ZIP/Postal Code

43005

Country

Ukraine

Facility Name

GSK Investigational Site

City

Lutsk

ZIP/Postal Code

43024

Country

Ukraine

Facility Name

GSK Investigational Site

City

Lviv

ZIP/Postal Code

79049

Country

Ukraine

Facility Name

GSK Investigational Site

City

Odesa

ZIP/Postal Code

65026

Country

Ukraine

Facility Name

GSK Investigational Site

City

Odessa

ZIP/Postal Code

65025

Country

Ukraine

Facility Name

GSK Investigational Site

City

Poltava

ZIP/Postal Code

36011

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsia

ZIP/Postal Code

21001

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsia

ZIP/Postal Code

21018

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsia

ZIP/Postal Code

21029

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsia

ZIP/Postal Code

21050

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsya

ZIP/Postal Code

21029

Country

Ukraine

Facility Name

GSK Investigational Site

City

Zaporizhzhia

ZIP/Postal Code

69014

Country

Ukraine

Facility Name

GSK Investigational Site

City

Zaporizhzia

ZIP/Postal Code

69065

Country

Ukraine

Facility Name

GSK Investigational Site

City

Zhytomyr

ZIP/Postal Code

10002

Country

Ukraine

Facility Name

GSK Investigational Site

City

Romford

State/Province

Essex

ZIP/Postal Code

RM1 3PJ

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Northwood

State/Province

Middlesex

ZIP/Postal Code

HA6 2RN

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Kenilworth

State/Province

Warwickshire

ZIP/Postal Code

CV8 1JD

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

http://clinicalstudydatarequest.com

Links:

URL

https://clinicaltrials.gov/ct2/show/NCT04333147?term=209564&draw=2&rank=1

Description

209564 contRAst X NCT04333147

Learn more about this trial

Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

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Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (contRAst 1)

Arthritis, Rheumatoid

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial