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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 550
- 试验地点
- 1
- 主要终点
- Percentage of Participants With 20% Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double blinded
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GSK3196165 90 mg
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).
干预措施: GSK3196165 (Otilimab) (Biological)
GSK3196165 90 mg
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).
干预措施: csDMARDs (Drug)
GSK3196165 150 mg
Entire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.
干预措施: GSK3196165 (Otilimab) (Biological)
GSK3196165 150 mg
Entire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.
干预措施: csDMARDs (Drug)
Sarilumab 200 mg
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.
干预措施: Sarilumab (Biological)
Sarilumab 200 mg
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.
干预措施: Placebo to GSK3196165/ Sarilumab (Drug)
Sarilumab 200 mg
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.
干预措施: csDMARDs (Drug)
Placebo sequence 1
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.
干预措施: GSK3196165 (Otilimab) (Biological)
Placebo sequence 1
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.
干预措施: Placebo to GSK3196165/ Sarilumab (Drug)
Placebo sequence 1
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.
干预措施: csDMARDs (Drug)
Placebo sequence 2
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.
干预措施: GSK3196165 (Otilimab) (Biological)
Placebo sequence 2
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.
干预措施: Placebo to GSK3196165/ Sarilumab (Drug)
Placebo sequence 2
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.
干预措施: csDMARDs (Drug)
Placebo sequence 3
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.
干预措施: Sarilumab (Biological)
Placebo sequence 3
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.
干预措施: Placebo to GSK3196165/ Sarilumab (Drug)
Placebo sequence 3
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.
干预措施: csDMARDs (Drug)
结局指标
主要结局
Percentage of Participants With 20% Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo
时间窗: Week 12
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.
次要结局
- 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(Week 24)
- Percentage of Participants With DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12(Week 12)
- Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- 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(Week 24)
- Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12(Week 12)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) (Versus Placebo) at Week 12(Baseline (Day 01) and Week 12)
- Percentage of Participants With Clinical Disease Activity Index (CDAI) Total Score <=10 (CDAI Low Disease Activity [LDA]) at Week 12(Week 12)
- Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- Change From Baseline in CDAI Total Score at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in CDAI Total Score at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in CDAI Total Score at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Change From Baseline in Arthritis Pain Visual Analogue Scale (VAS) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in Arthritis Pain VAS at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in Arthritis Pain VAS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 12(Week 12)
- Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- 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(Week 24)
- Percentage of Participants With ACR20 at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With ACR20 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- Percentage of Participants With 50% Improvement in American College of Rheumatology Criteria (ACR50) at Week 12(Week 12)
- Percentage of Participants With ACR50 at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With ACR50 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- Percentage of Participants With 70% Improvement in American College of Rheumatology Criteria (ACR70) at Week 12(Week 12)
- Percentage of Participants With ACR70 at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With ACR70 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- 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(Week 12)
- Percentage of Participants With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- 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(Week 24)
- Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) at Week 12(Week 12)
- Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- Percentage of Participants With a Good/Moderate European League Against Rheumatism (EULAR) Response at Week 12(Week 12)
- Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- Percentage of Participants With ACR/EULAR Remission at Week 12(Week 12)
- Percentage of Participants With ACR/EULAR Remission at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Week 24)
- Percentage of Participants With ACR/EULAR Remission at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Week 24)
- Change From Baseline in DAS28-CRP and DAS28-ESR at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Change From Baseline in HAQ-DI at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in HAQ-DI at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in FACIT-Fatigue at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in FACIT-Fatigue at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Change From Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in SF-36 PCS at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in SF-36 PCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in SF-36 MCS at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in SF-36 MCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Change From Baseline in SF-36 Domain Scores at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in SF-36 Domain Scores at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in SF-36 Domain Scores at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Day 01) and Week 24)
- Incidence of Adverse Events (AEs), Serious Adverse Event (SAEs), Adverse Events of Special Interest (AESI)(Up to Week 24)
- Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- 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(Baseline (Day 01) and Week 24)
- Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- 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(Baseline (Week 12) and Week 24)
- Change From Baseline in White Blood Cell (WBC) Count (Giga Cells Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Week 12) and Week 24)
- Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Week 12) and Week 24)
- 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(Baseline (Day 01) and Week 12)
- 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(Baseline (Day 01) and Week 24)
- 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(Baseline (Week 12) and Week 24)
- Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Week 12) and Week 24)
- Change From Baseline in Albumin Level (Grams Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Week 12) and Week 24)
- Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12(Baseline (Week 12) and Week 24)
- Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody(At baseline)
- Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol (Millimoles Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- 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(Baseline (Day 01) and Week 24)
- 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(Baseline (Week 12) and Week 24)
- Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1(Baseline (Day 01) and Week 24)
- 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(Baseline (Week 12) and Week 24)
- Number of Participants With Anti-GSK3196165 Antibodies(Up to Week 24)
- Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 12(Baseline (Day 01) and Week 12)
- 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(Up to Week 24)