IL1T-AI-0505: A Multi-center, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, & Efficacy of Rilonacept in Subjects With Cryopyrin-Associated Periodic Syndromes (CAPS) Using Parallel Group & Randomized Withdrawal Designs
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 104
- 主要终点
- Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)
研究概览
简要总结
Inflammatory symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) are due to mutations in a the NLRP-3 gene (previously known as Cold Induced Autoinflammatory Syndrome-1 or CIAS1). These mutations result in the body's overproduction of interleukin-1 (IL-1), a protein that stimulates the inflammatory process. IL-1 Trap (rilonacept) was designed to bind to the interleukin-1 cytokine and prevent it from binding to its receptors in the body.
详细描述
Primary Objective:
The primary objective of this study was to assess the effect of rilonacept on the clinical signs and symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) when used for chronic therapy as evaluated by the subjects themselves over time using a validated patient-reported outcomes tool.
Secondary Objective(s):
The secondary objectives were as follows:
- To determine the safety and tolerability of rilonacept in subjects with CAPS
- To assess the effect of rilonacept on laboratory measures of inflammation such as acute phase reactants
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
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Double-blind phases: adults age 18 and above; Open-label extension: Adults and children aged 7 years and older.
- •Was diagnosed with Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS) based upon clinical signs and symptoms
- •Had documented mutation in NLRP-3 (Cold Induced Autoinflammatory Syndrome-1 or CIAS1) in subject or relative, and willingness to have a confirmatory genetic (Deoxyribonucleic acid or DNA) test (cheek swab).
- •Was able to understand and comply with study procedures and was able to provide informed consent
- •If female, was not currently pregnant and was willing to use contraception during the study
排除标准
- •Had evidence of untreated tuberculosis or other conditions/therapies that made the subject inappropriate for this study.
研究组 & 干预措施
Placebo
Some subjects were treated with Placebo in the Study. This occurred (if subject randomized to Placebo) either during the first 6 weeks of the study or during the randomized withdrawal (weeks 15-24).
干预措施: Placebo (Drug)
rilonacept 160 mg
If randomized to rilonacept, subjects received this treatment during the first 6 weeks of the study or during the randomized withdrawal (weeks 15-24). All subjects received rilonacept 160 mg during weeks 6-14 (between Parts A and B).
Study drug is administered as a 2.0 mL subcutaneous injection once a week. At baseline (week 0) subjects receive a loading dose of rilonacept 320 mg.
干预措施: rilonacept 160 mg (Drug)
Open-Label rilonacept 160 mg
After week 24 (the end of part B), all subjects went into weekly dosing of open label rilonacept 160 mg. During this phase of the study, adolescents aged 7 and above were entered into the study and rilonacept was dosed as 2.2 mg/kg injections, up to 160 mg, per week.
Study drug is administered as a 2.0 mL subcutaneous injection once a week.
干预措施: rilonacept 160 mg (Drug)
结局指标
主要结局
Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)
时间窗: Baseline (Days -21 to -1) and Week 6 (Days 21-42)
The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue). KSS was averaged over two 21-day daily reporting periods (the 3 weeks prior to both baseline and week 6). In part A, a negative change in mean values indicated improvement under treatment with rilonacept in symptoms. The DHAF was used because it is a validated instrument to collect subject's self-reported responses.
Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)
时间窗: Week 15 through Week 24 (randomized withdrawal)
The mean Key Symptom Score (KSS --from the validated, patient-administered DHAF) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue). Subjects all received rilonacept 160 mg from week 6 through week 14. At week 15, subjects were re-randomized in a 1:1 ratio between Placebo and rilonacept 160 mg. Subjects baseline period was the 21-day period prior to week 15 randomization. A positive score indicated a worsening of symptoms versus an active treatment rilonacept baseline period.
次要结局
未报告次要终点