Back to results

Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors (contRAst 3)

Primary Purpose

Arthritis, Rheumatoid

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

GSK3196165 (Otilimab)

Sarilumab

Placebo to GSK3196165/ Sarilumab

csDMARDs

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring bDMARD, GSK3196165, Rheumatoid Arthritis, Sarilumab, Otilimab

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 joints (tender joint count [TJC]), and
- >=6/66 swollen joints (swollen joint count [SJC])
Has had an inadequate response despite currently taking at least one and at the most two concomitant csDMARDs for at least 12 weeks, from the following:
- Methotrexate (MTX)
- Hydroxychloroquine or chloroquine
- Sulfasalazine
- Leflunomide
- Bucillamine
- Iguratimod
- Tacrolimus
Has had inadequate response to at least one bDMARD at an approved dose and/or at least one JAK inhibitors at an approved dose. In both cases this may be with or without combination with a csDMARD.
- If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC.

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.
Has known infection with human immunodeficiency virus (HIV) or current acute or chronic hepatitis B and/or hepatitis C.

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 90 mg

GSK3196165 150 mg

Sarilumab 200 mg

Placebo sequence 1

Placebo sequence 2

Placebo sequence 3

Arm Description

Entire treatment period (24 Weeks): GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).

Entire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Entire treatment period (24 Weeks): Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.

Outcomes

Primary Outcome Measures

Percentage of Participants With 20% 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 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

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

Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily living activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. Overall HAQ-DI score was computed as the 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. 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 With Clinical Disease Activity Index (CDAI) Total Score <=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 (TJC28), 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). 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.

Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Treatment Arms That 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 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.

Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.

Change From Baseline in CDAI Total Score at Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. A negative CDAI total score change from baseline indicates an improvement in disease activity. 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 for Treatment Arms That Started Study Intervention From Day 1

Change From Baseline in CDAI Total Score at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Change From Baseline in Arthritis Pain Visual Analogue Scale (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. 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 for Treatment Arms That Started Study Intervention From Day 1

Change From Baseline in Arthritis Pain VAS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With 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 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. 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 With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With ACR20 at Week 24 for Treatment Arms That Started Study Intervention From Day 1

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

Percentage of Participants With ACR20 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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

ACR50 is calculated as a 50% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50% 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 With ACR50 at Week 24 for Treatment Arms That Started Study Intervention From Day 1

ACR50 is calculated as a 50% improvement from Baseline in TJC68 and SJC66 and a 50% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).

Percentage of Participants With ACR50 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With 70% Improvement in American College of Rheumatology Criteria (ACR70) at Week 12

ACR70 is calculated as a 70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 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 With ACR70 at Week 24 for Treatment Arms That Started Study Intervention From Day 1

ACR70 is calculated as a 70% improvement from Baseline in TJC68 and SJC66 and a 70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).

Percentage of Participants With ACR70 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With 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 indicates 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. 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 With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Treatment Arms That 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 indicates 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 With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From 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 indicates 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 With 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 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. 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 With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With 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 indicates less disease activity. Remission is achieved when DAS28-CRP <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 With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

The DAS28-CRP arthritis 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 indicates less disease activity. Remission is achieved when DAS28-CRP <2.6. A negative change from baseline in DAS28-CRP indicates an improvement.

Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With 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 indicates 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 With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Treatment Arms That Started Study Intervention From Day 1

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 indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.

Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Placebo Switched Arms That Started Study Intervention From 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 indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.

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

DAS28-CRP and DAS28-ESR scores categorized using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1). 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 With a Good/Moderate EULAR Response at Week 24 for Treatment Arms That Started Study Intervention From Day 1

DAS28-CRP and DAS28-ESR scores categorised using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1).

Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Percentage of Participants With 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.

Percentage of Participants With ACR/EULAR Remission at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Percentage of Participants With ACR/EULAR Remission at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) 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. 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 and DAS28-ESR at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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

Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. 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=least difficulty to 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement.

Change From Baseline in HAQ-DI at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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. 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 for Treatment Arms That Started Study Intervention From Day 1

Change From Baseline in FACIT-Fatigue at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Change From Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12

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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregate score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical heath. Quality Metrics software was used for scoring for SF-36. 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 for Treatment Arms That Started Study Intervention From Day 1

Change From Baseline in SF-36 PCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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

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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36. 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 MCS at Week 24 for Treatment Arms That 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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.

Change From Baseline in SF-36 MCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.

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

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 scaled between 0 to 100, where higher score represents better health. A positive change from baseline 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.

Change From Baseline in SF-36 Domain Scores at Week 24 for Treatment Arms That 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 scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.

Change From Baseline in SF-36 Domain Scores at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

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 scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.

Incidence of Adverse Events (AEs), Serious Adverse Event (SAEs), Adverse Events of Special Interest (AESI)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death.

Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count. 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 Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.

Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.

Change From Baseline in White Blood Cell (WBC) Count (Giga Cells Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count. 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 (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.

Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.

Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 12

Blood samples was collected for the assessment of change from baseline in hematology parameter hemoglobin level. 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 Hemoglobin Level (Grams Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.

Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.

Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP) Gamma-glutamyl Transferase(GGT) Levels (International Units Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in laboratory parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) gamma-glutamyl transferase (GGT) levels. 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 AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.

Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.

Change From Baseline in Albumin Level (Grams Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level. 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 Albumin Level (Grams Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.

Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.

Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in laboratory parameter total bilirubin level. 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 Total Bilirubin (Micromoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.

Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.

Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels. 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 Total Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.

Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.

Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol (Millimoles Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels. 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 Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.

Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.

Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 12

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. 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 Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.

Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.

Number of Participants With National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities for Treatment Arms That Started Study Intervention From Day 1

Number of participants who reported NCI-CTCAE Grade 3 or higher for hematological and clinical chemistry abnormalities were summarized.

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

Blood samples were collected for markers which may influence rheumatoid arthritis. Concentrations of GM-CSF autoantibodies was determined.

Number of Participants With Anti-GSK3196165 Antibodies

Blood samples were collected for anti-GSK3196165 antibodies detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis.

Full Information

NCT ID

NCT04134728

First Posted

October 18, 2019

Last Updated

July 11, 2023

Sponsor

GlaxoSmithKline

Collaborators

Iqvia Pty Ltd

1. Study Identification

Unique Protocol Identification Number

NCT04134728

Brief Title

Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors

Acronym

contRAst 3

Official Title

A 24-week, Phase 3, Multicentre, Randomised, Double-blind, Efficacy and Safety Study, Comparing GSK3196165 With Placebo and With Sarilumab, in Combination With Conventional Synthetic DMARDs, in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological DMARDs and/or Janus Kinase Inhibitors

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

October 31, 2019 (Actual)

Primary Completion Date

September 15, 2021 (Actual)

Study Completion Date

February 1, 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 3 [202018: NCT04134728]) is a Phase 3, randomized, multicenter, double-blind study to assess the safety and efficacy of GSK3196165 in combination with conventional (cs) DMARD[s]) or the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to biologic (b) DMARD[s]) and/or JAK inhibitors. The study will consist of a screening phase of up to 6 weeks followed by 24 week treatment phase in which participants will be randomized in ratio of 6:6:6:1:1:1 to GSK3196165 150 milligrams (mg) subcutaneously (SC) weekly,GSK3196165 90 mg SC weekly, sarilumab 200 mg SC every other week or placebo (three arms) respectively, all in combination with background csDMARD(s). At Week 12, participants in the three placebo arms will switch from placebo to active intervention (either GSK3196165 150 mg SC weekly, GSK3196165 90 mg SC weekly, or sarilumab 200 mg SC every other week). 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]). Any participant who does not transition into study 209564 will undergo a safety follow-up visit at Week 34 (corresponding to 12 weeks after the last potential dose of sarilumab, at Week 22).

6. Conditions and Keywords

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

Arthritis, Rheumatoid

Keywords

bDMARD, GSK3196165, Rheumatoid Arthritis, Sarilumab, Otilimab

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 6:6:6:1:1:1

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Double blinded

Allocation

Randomized

Enrollment

550 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GSK3196165 90 mg

Arm Type

Experimental

Arm Description

Entire treatment period (24 Weeks): GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).

Arm Title

GSK3196165 150 mg

Arm Type

Experimental

Arm Description

Entire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Arm Title

Sarilumab 200 mg

Arm Type

Active Comparator

Arm Description

Entire treatment period (24 Weeks): Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.

Arm Title

Placebo sequence 1

Arm Type

Placebo Comparator

Arm Description

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Arm Title

Placebo sequence 2

Arm Type

Placebo Comparator

Arm Description

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Arm Title

Placebo sequence 3

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

Biological

Intervention Name(s)

Sarilumab

Intervention Description

Sarilumab solution in PFS to be administered SC.

Intervention Type

Drug

Intervention Name(s)

Placebo to GSK3196165/ Sarilumab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

csDMARDs

Intervention Description

Stable dose of csDMARD(s) as SoC.

Primary Outcome Measure Information:

Title

Percentage of Participants With 20% 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

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

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Percentage of Participants With Clinical Disease Activity Index (CDAI) Total Score <=10 (CDAI Low Disease Activity [LDA]) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Treatment Arms That 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 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.

Time Frame

Week 24

Title

Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.

Time Frame

Week 24

Title

Change From Baseline in CDAI Total Score at Week 12

Description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. A negative CDAI total score change from baseline indicates an improvement in disease activity. 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 01) and Week 12

Title

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

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in CDAI Total Score at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Arthritis Pain Visual Analogue Scale (VAS) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

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

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Arthritis Pain VAS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Percentage of Participants With 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 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. 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 With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

Percentage of Participants With ACR20 at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With ACR20 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 12

Title

Percentage of Participants With ACR50 at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With ACR50 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

Percentage of Participants With 70% Improvement in American College of Rheumatology Criteria (ACR70) at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants With ACR70 at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With ACR70 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

Percentage of Participants With 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 With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Treatment Arms That 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 indicates 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

Title

Percentage of Participants With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From 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 indicates 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

Title

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

Description

Time Frame

Week 12

Title

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

Description

Time Frame

Week 24

Title

Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

Percentage of Participants With 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 indicates less disease activity. Remission is achieved when DAS28-CRP <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 With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

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

Description

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 indicates 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.

Time Frame

Week 12

Title

Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

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 indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.

Time Frame

Week 24

Title

Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

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 indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.

Time Frame

Week 24

Title

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

Description

Time Frame

Week 12

Title

Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

Percentage of Participants With ACR/EULAR Remission at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants With ACR/EULAR Remission at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Time Frame

Week 24

Title

Percentage of Participants With ACR/EULAR Remission at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Baseline (Day 01) and Week 12

Title

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

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Baseline (Day 01) and Week 24

Title

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

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in HAQ-DI at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Baseline (Day 01) and Week 24

Title

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

Description

Time Frame

Baseline (Day 01) and Week 12

Title

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

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in FACIT-Fatigue at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

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

Description

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in SF-36 PCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Time Frame

Baseline (Day 01) and Week 24

Title

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

Description

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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36. 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 01) and Week 12

Title

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

Description

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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in SF-36 MCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

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 score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.

Time Frame

Baseline (Day 01) and Week 24

Title

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

Description

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 scaled between 0 to 100, where higher score represents better health. A positive change from baseline 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

Baseline (Day 01) and Week 12

Title

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

Description

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 scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in SF-36 Domain Scores at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

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 scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.

Time Frame

Baseline (Day 01) and Week 24

Title

Incidence of Adverse Events (AEs), Serious Adverse Event (SAEs), Adverse Events of Special Interest (AESI)

Description

Time Frame

Up to Week 24

Title

Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in White Blood Cell (WBC) Count (Giga Cells Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP) Gamma-glutamyl Transferase(GGT) Levels (International Units Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Albumin Level (Grams Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol (Millimoles Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.

Time Frame

Baseline (Week 12) and Week 24

Title

Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 12

Description

Time Frame

Baseline (Day 01) and Week 12

Title

Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.

Time Frame

Baseline (Week 12) and Week 24

Title

Description

Number of participants who reported NCI-CTCAE Grade 3 or higher for hematological and clinical chemistry abnormalities were summarized.

Time Frame

Up to Week 24

Title

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

Description

Blood samples were collected for markers which may influence rheumatoid arthritis. Concentrations of GM-CSF autoantibodies was determined.

Time Frame

At baseline

Title

Number of Participants With Anti-GSK3196165 Antibodies

Description

Blood samples were collected for anti-GSK3196165 antibodies detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis.

Time Frame

Up to Week 24

Other Pre-specified Outcome Measures:

Title

Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 12

Description

Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels. 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 01) and Week 12

Title

Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1

Description

Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels.

Time Frame

Baseline (Day 01) and Week 24

Title

Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12

Description

Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels.

Time Frame

Baseline (Week 12) and Week 24

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 joints (tender joint count [TJC]), and >=6/66 swollen joints (swollen joint count [SJC]) Has had an inadequate response despite currently taking at least one and at the most two concomitant csDMARDs for at least 12 weeks, from the following: Methotrexate (MTX) Hydroxychloroquine or chloroquine Sulfasalazine Leflunomide Bucillamine Iguratimod Tacrolimus Has had inadequate response to at least one bDMARD at an approved dose and/or at least one JAK inhibitors at an approved dose. In both cases this may be with or without combination with a csDMARD. If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC. 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. Has known infection with human immunodeficiency virus (HIV) or current acute or chronic hepatitis B and/or hepatitis C.

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

Mesa

State/Province

Arizona

ZIP/Postal Code

85210

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

Tujunga

State/Province

California

ZIP/Postal Code

91042

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

DeBary

State/Province

Florida

ZIP/Postal Code

32713

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

33134

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

Atlanta

State/Province

Georgia

ZIP/Postal Code

30318

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

Skokie

State/Province

Illinois

ZIP/Postal Code

60076

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

Lebanon

State/Province

New Hampshire

ZIP/Postal Code

03756

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

73104

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

Austin

State/Province

Texas

ZIP/Postal Code

78731

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

77065

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

Houston

State/Province

Texas

ZIP/Postal Code

77090

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

Plano

State/Province

Texas

ZIP/Postal Code

75024

Country

United States

Facility Name

GSK Investigational Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

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

Tomball

State/Province

Texas

ZIP/Postal Code

77375

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

C1046AAQ

Country

Argentina

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

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

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

San Juan

ZIP/Postal Code

5400

Country

Argentina

Facility Name

GSK Investigational Site

City

Mons

ZIP/Postal Code

7000

Country

Belgium

Facility Name

GSK Investigational Site

City

Barrie

State/Province

Ontario

ZIP/Postal Code

L4M 6L2

Country

Canada

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

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 11

ZIP/Postal Code

148 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 2

ZIP/Postal Code

128 50

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

Rendsburg

State/Province

Schleswig-Holstein

ZIP/Postal Code

24768

Country

Germany

Facility Name

GSK Investigational Site

City

Hamburg

ZIP/Postal Code

D-20095

Country

Germany

Facility Name

GSK Investigational Site

City

Magdeburg

ZIP/Postal Code

39120

Country

Germany

Facility Name

GSK Investigational Site

City

Budapest

ZIP/Postal Code

1023

Country

Hungary

Facility Name

GSK Investigational Site

City

Szekesfehervar

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

Verona

State/Province

Veneto

ZIP/Postal Code

37126

Country

Italy

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

455-8530

Country

Japan

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

457-8511

Country

Japan

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

460-0001

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

270-2296

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

807-8555

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

060-8648

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

063-0811

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

673-1462

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

675-1392

Country

Japan

Facility Name

GSK Investigational Site

City

Ibaraki

ZIP/Postal Code

312-0057

Country

Japan

Facility Name

GSK Investigational Site

City

Kagoshima

ZIP/Postal Code

891-0133

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

245-8575

Country

Japan

Facility Name

GSK Investigational Site

City

Kochi

ZIP/Postal Code

781-0112

Country

Japan

Facility Name

GSK Investigational Site

City

Kumamoto

ZIP/Postal Code

862-0976

Country

Japan

Facility Name

GSK Investigational Site

City

Miyagi

ZIP/Postal Code

980-8574

Country

Japan

Facility Name

GSK Investigational Site

City

Nagasaki

ZIP/Postal Code

857-1195

Country

Japan

Facility Name

GSK Investigational Site

City

Saitama

ZIP/Postal Code

359-1111

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

104-8560

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

142-0054

Country

Japan

Facility Name

GSK Investigational Site

City

Incheon

ZIP/Postal Code

400-711

Country

Korea, Republic of

Facility Name

GSK Investigational Site

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

GSK Investigational Site

City

Seoul

ZIP/Postal Code

04763

Country

Korea, Republic of

Facility Name

GSK Investigational Site

City

Seoul

ZIP/Postal Code

3080

Country

Korea, Republic of

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

Bialystok

ZIP/Postal Code

15-879

Country

Poland

Facility Name

GSK Investigational Site

City

Bydgoszcz

ZIP/Postal Code

85-168

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

81-537

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

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

Torun

ZIP/Postal Code

87-100

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

Pretoria

State/Province

Gauteng

ZIP/Postal Code

184

Country

South Africa

Facility Name

GSK Investigational Site

City

Durban

State/Province

KwaZulu- Natal

ZIP/Postal Code

4319

Country

South Africa

Facility Name

GSK Investigational Site

City

Cape Town

ZIP/Postal Code

7500

Country

South Africa

Facility Name

GSK Investigational Site

City

Kempton Park

ZIP/Postal Code

1619

Country

South Africa

Facility Name

GSK Investigational Site

City

Pretoria

ZIP/Postal Code

0002

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

Elche

ZIP/Postal Code

03203

Country

Spain

Facility Name

GSK Investigational Site

City

Santander

ZIP/Postal Code

39008

Country

Spain

Facility Name

GSK Investigational Site

City

Santiago de Compostela

ZIP/Postal Code

15706

Country

Spain

Facility Name

GSK Investigational Site

City

Valencia

ZIP/Postal Code

46010

Country

Spain

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

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

We'll reach out to this number within 24 hrs

Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors (contRAst 3)

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