A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 546
- 试验地点
- 196
- 主要终点
- Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24
研究概览
简要总结
Primary Objective:
To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were effective for:
- reduction of signs and symptoms at Week 24 and
- improvement of physical function at Week 12
in participants with active rheumatoid arthritis (RA) who were inadequate responders or intolerant to tumor necrosis factor alpha (TNF-α) antagonists.
Secondary Objectives:
The secondary objectives were to investigate the effects of SAR153191 (REGN88) when added to DMARD therapy, in participants with active RA who were inadequate responders or intolerant to TNF-α antagonists, for:
- Reduction of signs and symptoms at Week 12;
- Improvement in physical function at Week 24;
- Improvement in disease activity score as measured by other American College of Rheumatology (ACR) derived components at Weeks 12 and 24;
- Improvement in quality of life as measured by participant reported outcomes (PROs) at intermediate visits and Week 24.
To assess the exposure of sarilumab added to DMARD therapy in this population.
To assess the safety of sarilumab in this population.
详细描述
Total study duration was up to 34 weeks: screening up to 28 days, treatment phase of 24 weeks, and post-treatment follow-up of 6 weeks.
After completion of the treatment phase of this study, participant were eligible to enter a long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
Placebo q2w
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: placebo (Drug)
Placebo q2w
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: hydroxychloroquine (Drug)
Placebo q2w
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: methotrexate (Drug)
Placebo q2w
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: sulfasalazine (Drug)
Placebo q2w
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: leflunomide (Drug)
Sarilumab 150 mg q2w
Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: sulfasalazine (Drug)
Sarilumab 150 mg q2w
Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: Sarilumab (Drug)
Sarilumab 150 mg q2w
Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: hydroxychloroquine (Drug)
Sarilumab 150 mg q2w
Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: methotrexate (Drug)
Sarilumab 150 mg q2w
Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: leflunomide (Drug)
Sarilumab 200 mg q2w
Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: Sarilumab (Drug)
Sarilumab 200 mg q2w
Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: hydroxychloroquine (Drug)
Sarilumab 200 mg q2w
Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: methotrexate (Drug)
Sarilumab 200 mg q2w
Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: sulfasalazine (Drug)
Sarilumab 200 mg q2w
Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
干预措施: leflunomide (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24
时间窗: Week 24
ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels \[CRP\]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index \[HAQ-DI\]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
时间窗: Baseline, Week 12
Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.
次要结局
- Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24(Baseline, Week 24)
- Percentage of Participants Achieving ACR50 Criteria at Week 24(Week 24)
- Percentage of Participants Achieving ACR70 Criteria at Week 24(Week 24)
- Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24(Week 24)
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24(Baseline, Week 24)
- Change From Baseline in HAQ-DI at Week 24(Baseline, Week 24)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24(Baseline, Week 24)
- Change From Baseline in SF-36 MCS at Week 24(Baseline, Week 24)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24(Baseline, Week 24)
- Change From Baseline in Morning Stiffness VAS at Week 24(Baseline, Week 24)
- Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA(Baseline, Week 24)
- Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity(Baseline, Week 24)
- Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24(Baseline, Week 24)
- Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24(Baseline, Week 24)
- Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12(Week 12)
- Change From Baseline in DAS28-CRP at Week 12(Baseline, Week 12)
- Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12(Week 12)
- Change From Baseline in SF-36 at Week 12(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA(Baseline, Week 12)
- Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity(Baseline, Week 12)
- Change From Baseline in the FACIT-fatigue at Week 12(Baseline, Week 12)
- Change From Baseline in EQ-5D-3L VAS Scores at Week 12(Baseline, Week 12)
- Change From Baseline in RAID Scores at Week 12(Baseline, Week 12)
- Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24(Baseline, Week 12 and Week 24)
- Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24(Baseline, Week 12 and Week 24)