An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered With Subcutaneous (SC) Injection, in Children and Adolescents, Aged 2 to 17 Years, With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) Followed by an Extension Phase
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 102
- 试验地点
- 30
- 主要终点
- Maximum Serum Concentration (Cmax) of Sarilumab at Week 12
研究概览
简要总结
Primary Objective:
To describe the pharmacokinetic (PK) profile of sarilumab in participants aged 2-17 years with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) in order to identify the dose and regimen for adequate treatment of this population
Secondary Objective:
To describe the pharmacodynamic (PD) profile, the efficacy and the long-term safety of sarilumab in participants with pcJIA.
详细描述
For 73 participants enrolled in the dose-finding and second portions, the total study duration per participant was up to 166 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 144-week extension phase, and a 6-week post-treatment follow-up. For 29 participants enrolled in the third portion, the total study duration per participant was up to 106 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 84-week extension phase, and a 6-week post-treatment follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 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
Sarilumab
Participants received one of three ascending dose regimens of sarilumab by subcutaneous (SC) injection based on body weight. All the participants received the selected dose regimen once this was identified. Sarilumab was given during 12-week core treatment phase followed by an extension treatment phase (144 weeks for 73 participants enrolled in dose-finding and second portions and 84 weeks for approximately 29 participants enrolled in third portion)
干预措施: Sarilumab (Drug)
结局指标
主要结局
Maximum Serum Concentration (Cmax) of Sarilumab at Week 12
时间窗: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
The Cmax was defined as maximum serum concentration. The values reported are mean and standard deviation.
Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12
时间窗: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
The AUC0-t was defined as area under the concentration in serum versus time curve calculated using the trapezoidal method during a dose interval (tau). The values reported are mean and standard deviation.
Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12
时间窗: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
The Ctrough was defined as concentration observed before treatment administration during repeated dosing from baseline to Week 12. The values reported are mean and standard deviation.
次要结局
- Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Change From Baseline in Interleukin-6 (IL-6) at Week 12(Baseline (Day 1) and Week 12)
- Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12(Baseline (Day 1) and Week 12)
- Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12(Week 12)
- Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156(Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12(Week 12)
- Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156(Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12(Week 12)
- Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156(Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12(Week 12)
- Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156(Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12(Week 12)
- Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156(Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12(Baseline (Day 1) and Week 12)
- Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156(Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)(From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3)
- Number of Participants With Local Site Reactions(From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3)