A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 118
- 试验地点
- 84
- 主要终点
- Percentage of Participants Achieving Sustained Remission at Week 52
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of KEVZARA (sarilumab) in participants with polymyalgia rheumatica (PMR) as assessed by the proportion of participants with sustained remission for sarilumab with a shorter corticosteroid (CS) tapering regimen as compared to placebo with a longer CS tapering regimen.
Secondary Objectives:
- To demonstrate the efficacy of sarilumab in participants with PMR compared to placebo, in combination with a CS taper with regards to:
- Clinical responses (such as components of sustained remission, disease remission rates, time to first disease flare) over time.
- Cumulative CS (including prednisone) exposure.
- To assess the safety (including immunogenicity) and tolerability of sarilumab in participants with PMR.
- To measure sarilumab serum concentrations in participants with PMR.
- To assess the effect of sarilumab in reducing glucocorticoid toxicity as measured by the composite glucocorticoid toxicity index (GTI) questionnaire.
详细描述
Study duration per participant was approximative 62 weeks including up to a 4-week screening period, 52-week treatment period and 6-week follow-up period.
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
- 50 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+52 Week Taper
Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.
干预措施: Sarilumab-matching placebo (Drug)
Placebo+52 Week Taper
Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.
干预措施: Prednisone (Drug)
Placebo+52 Week Taper
Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.
干预措施: Prednisone-matching placebo (Drug)
Sarilumab 200mg q2w+14 Week Taper
Participants received sarilumab 200 milligrams (mg) as SC injection q2w up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 14 weeks and prednisone-matching placebo from Week 14 up to Week 52.
干预措施: Sarilumab SAR153191 (REGN88) (Drug)
Sarilumab 200mg q2w+14 Week Taper
Participants received sarilumab 200 milligrams (mg) as SC injection q2w up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 14 weeks and prednisone-matching placebo from Week 14 up to Week 52.
干预措施: Prednisone (Drug)
Sarilumab 200mg q2w+14 Week Taper
Participants received sarilumab 200 milligrams (mg) as SC injection q2w up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 14 weeks and prednisone-matching placebo from Week 14 up to Week 52.
干预措施: Prednisone-matching placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving Sustained Remission at Week 52
时间窗: At Week 52
Sustained remission was defined as meeting all of the following parameters: achievement of disease remission (defined as resolution of signs and symptoms of polymyalgia rheumatica \[PMR\], and normalization of C-reactive protein \[CRP\] {less than \[\<\]10 milligrams per liter \[mg/L\]}) not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active PMR plus an increase in corticosteroid \[CS\] dose due to PMR or elevation of erythrocyte sedimentation rate \[ESR\] attributable to active PMR plus an increase in CS dose due to PMR) from Week 12 through Week 52, sustained reduction of CRP (to \<10 mg/L, with absence of successive elevations to greater than or equal to \[\>=\]10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52.
次要结局
- Time to First Polymyalgia Rheumatica Flare After Clinical Remission up to Week 52(Up to Week 52)
- Total Cumulative Corticosteroid Dose(Up to Week 52)
- Number of Participants Who Achieved Disease Remission up to Week 12(Up to Week 12)
- Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters(From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60))
- Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response(From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60))
- Number of Participants With Absence of Disease Flare From Week 12 Through Week 52(From Week 12 Through Week 52)
- Number of Participants With Sustained Reduction of CRP From Week 12 Through Week 52(From Week 12 through Week 52)
- Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52(From Week 12 through Week 52)
- Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 52(At Week 52)
- Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities During TEAE Period(From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose (i.e. Day 1) up to 60 days after last dose date of study drug (i.e. up to Week 60))
- Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameter(From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60))
- Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function(From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60))
- Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function(From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60))
- Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24(Post-dose at Week 24)
- Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab(Pre-dose on Week 0 (Baseline), Week 2, 4, 12, 16, 24, and 52)