A Randomized, Double-blind, Parallel-group Study Assessing the Efficacy and Safety of Sarilumab Monotherapy Versus Adalimumab Monotherapy in Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 369
- 试验地点
- 86
- 主要终点
- DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24
研究概览
简要总结
Primary Objective:
To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) in participants with active rheumatoid arthritis (RA) who were either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders.
Secondary Objectives:
To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy in participants with active RA who were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders, with respect to:
- Reduction of signs and symptoms of RA.
- Improvement in quality of life assessed by participant reported outcome questionnaires.
Assessment of the safety and tolerability of sarilumab monotherapy (including immunogenicity) throughout the study.
详细描述
Total study duration was up to 310 weeks: Up to a 4 week screening period, 24 week randomized double-blind treatment phase, 276-week open-label extension, and 6 weeks post-treatment final study visit.
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
Adalimumab 40 mg/Sarilumab 200 mg
Adalimumab 40 milligrams (mg) subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during the double-blind (DB) period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (less than [<] 20% improvement from baseline in tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in open label extension (OLE) period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
干预措施: Adalimumab (Drug)
Adalimumab 40 mg/Sarilumab 200 mg
Adalimumab 40 milligrams (mg) subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during the double-blind (DB) period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (less than [<] 20% improvement from baseline in tender joint count [TJC] and swollen joint count [SJC] for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in open label extension (OLE) period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
干预措施: Placebo (for sarilumab) (Drug)
Sarilumab 200 mg/Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
干预措施: Sarilumab (Drug)
Sarilumab 200 mg/Sarilumab 200 mg
Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).
干预措施: Placebo (for adalimumab) (Drug)
结局指标
主要结局
DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24
时间窗: Baseline, Week 24
DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR and RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Least square (LS) mean and standard error (SE) at Week 24 were obtained using Mixed-effect model with repeated measures (MMRM) approach.
次要结局
- DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24(Week 24)
- DB Period: Percentage of Participants Achieving ACR50 Criteria at Week 24(Week 24)
- DB Period: Percentage of Participants Achieving ACR70 Criteria at Week 24(Week 24)
- DB Period: Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24(Week 24)
- DB Period: Percentage of Participants Achieving ACR20 Criteria at Week 24(Week 24)
- DB Period: Change From Baseline in HAQ-DI at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24(Baseline, Week 24)
- DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24(Week 24)
- DB Period: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24(Week 24)
- DB Period: Change From Baseline in CDAI at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by >= 50% Due to Arthritis(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis(Baseline, Week 24)
- DB Period: Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity(Baseline, Week 24)
- DB Period: Change From Baseline in Morning Stiffness VAS at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Individual ACR Component - TJC and SJC at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Individual ACR Component - CRP Level at Week 24(Baseline, Week 24)
- DB Period: Change From Baseline in Individual ACR Component- ESR Level at Week 24(Baseline, Week 24)
- DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From Week 0 to Week 24)
- OLE Period: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events(From end of Week 24 (Baseline of OLE Period) up to last dose in OLE + 6 weeks of follow up (i.e. up to Week 306))
- DB Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - Hematological Parameters(From Week 0 to Week 24)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein (HDL)(From Week 0 to Week 24)
- OLE Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameters(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities(From Week 0 to Week 24)
- OLE Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities(From end of Week 24 (Baseline of OLE Period) up to Week 300)
- DB Period: Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody (ADA) Response(From Week 0 to Week 24)
- Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody Response During Entire Treatment-emergent Adverse Event Period(From Week 0 up to last dose in OLE + 6 weeks of follow-up (i.e. up to Week 306))
- DB Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab(Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, and 24)
- OLE Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab(Pre-dose at Week 24 (Baseline of OLE period), 36, 48, 60, 84, 108, 132, 156, 180, 204, 228, 252, 276, 300 and 306)