A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Giant Cell Arteritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 83
- 试验地点
- 61
- 主要终点
- Percentage of Participants Who Achieved Sustained Disease Remission at Week 52
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of sarilumab in participants with giant cell arteritis (GCA) as assessed by the proportion of participants with sustained remission for sarilumab compared to placebo, in combination with a corticosteroid (CS) tapering course.
Secondary Objective:
- To demonstrate the efficacy of sarilumab in participants with GCA compared to placebo, in combination with CS taper with regards to:
- Clinical responses (such as responses based on 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 GCA.
- To measure sarilumab serum concentrations in participants with GCA.
- To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by glucocorticoid toxicity index (GTI).
详细描述
Study duration per participant was approximately 82 weeks, including an up to 6-week screening period, 52-week treatment period, and 24-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)
Placebo+26 Week Taper
Participants received sarilumab-matching placebo 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 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Sarilumab matching placebo (Drug)
Placebo+26 Week Taper
Participants received sarilumab-matching placebo 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 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Prednisone (Drug)
Placebo+26 Week Taper
Participants received sarilumab-matching placebo 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 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Prednisone matching placebo (Drug)
Sarilumab 150mg q2w+26 Week Taper
Participants received sarilumab 150 milligrams (mg) as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Sarilumab SAR153191 (Drug)
Sarilumab 150mg q2w+26 Week Taper
Participants received sarilumab 150 milligrams (mg) as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Prednisone (Drug)
Sarilumab 150mg q2w+26 Week Taper
Participants received sarilumab 150 milligrams (mg) as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Prednisone matching placebo (Drug)
Sarilumab 200mg q2w+26 Week Taper
Participants received sarilumab 200 mg as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Sarilumab SAR153191 (Drug)
Sarilumab 200mg q2w+26 Week Taper
Participants received sarilumab 200 mg as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Prednisone (Drug)
Sarilumab 200mg q2w+26 Week Taper
Participants received sarilumab 200 mg as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.
干预措施: Prednisone matching placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Sustained Disease Remission at Week 52
时间窗: At Week 52
Disease remission was defined as resolution of signs and symptoms of giant cell arteries (GCA), and normalization of C-reactive protein (CRP) (\<10 mg/L). Sustained remission was defined as meeting all of the following parameters: achievement of disease remission not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active GCA plus an increase in corticosteroid \[CS\] dose due to GCA or elevation of erythrocyte sedimentation rate \[ESR\] attributable to active GCA plus an increase in CS dose due to GCA) from Week 12 through Week 52, normalization of CRP (to \<10 mg/L, with absence of successive elevations to \>=10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52.
Percentage of Participants Who Achieved Sustained Disease Remission at Week 24
时间窗: At Week 24
Disease remission was defined as resolution of signs and symptoms of GCA, and normalization of CRP \<10 mg/L. Sustained remission was defined as meeting all of the following parameters: achievement of disease remission not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active GCA plus an increase in CS dose due to GCA, or elevation of ESR attributable to active GCA plus an increase in CS dose due to GCA) from Week 12 through Week 24, normalization of CRP (to \<10 mg/L, with an absence of successive elevations to \>=10 mg/L) from Week 12 through Week 24, and successful adherence to the prednisone taper from Week 12 through Week 24.
次要结局
- Number of Participants With Achievement of Disease Remission up to Week 12: Week 52 Analysis Set(Up to Week 12)
- Number of Participants With Achievement of Disease Remission up to Week 12: Intent-to-treat (ITT) Population(Up to Week 12)
- Number of Participants With Absence of Disease Flare From Week 12 Through Week 52: Week 52 Analysis Set(From Week 12 through Week 52)
- Number of Participants With Absence of Disease Flare From Week 12 Through Week 24: ITT Population(From Week 12 through Week 24)
- Number of Participants With Normalization of C-Reactive Protein From Week 12 Through Week 52: Week 52 Analysis Set(From Week 12 through Week 52)
- Number of Participants With Normalization of C-Reactive Protein (CRP) From Week 12 Through Week 24: ITT Population(From Week 12 through Week 24)
- Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52: Week 52 Analysis Set(From Week 12 through Week 52)
- Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 24: ITT Population(From Week 12 through Week 24)
- Total Cumulative Corticosteroid (Including Prednisone) Dose(Up to Week 52)
- Time to First Giant Cell Arteritis Disease Flare(Up to Week 52)
- Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 24: ITT Population(At Week 24)
- Composite Glucocorticoid Toxicity Index: Cumulative Worsening Score and Aggregate Improvement Score at Week 52(At Week 52)
- 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 (i.e., up to Week 60))
- Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab(Pre-dose on Week 0 (Baseline), Weeks 2, 4, 12, 16, 24 and 52)
- Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24(post-dose at Week 24)
- Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response(From Day 1 (Baseline) up to last dose date of study drug + 60 days (i.e., up to Week 60))
- Pharmacodynamics: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52(Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52)
- Pharmacodynamics: Change From Baseline in C-reactive Protein (CRP) Level at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52(Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52)
- Pharmacodynamics: Change From Baseline in Interleukin-6 (IL-6) at Weeks 2, 12, 24, and 52(Baseline, Weeks 2, 12, 24, and 52)
- Pharmacodynamics: Change From Baseline in Soluble Interleukin-6 Receptor (sIL-6R) Level at Weeks 2, 12, 24, and 52(Baseline, Weeks 2, 12, 24, and 52)