A Three-part,Multicenter Study,With a Randomized,Double-blind,Placebo Controlled,Withdrawal Design in Part II to Assess Efficacy,Safety,and Tolerability of ACZ885(Anti-interleukin-1beta Monoclonal Antibody)in Patients With Muckle-Wells Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
研究概览
简要总结
This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome.
Part I is an 8-week open-label, active treatment period to identify ACZ885 responders.
Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo.
Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II.
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
- 4 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome.
- •Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study, will have the option to participate in this study upon disease flare
- •Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy).
排除标准
- •History of being immunocompromised, including a positive HIV at screening test result.
- •No live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
- •History of significant medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial.
- •History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
- •Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Part I, Part II-arm1, & Part III
干预措施: ACZ885 (Drug)
Part II - arm 2
干预措施: Placebo (Drug)
结局指标
主要结局
Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
时间窗: 32 weeks after study start
Determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Data expressed as a percent of participants who had experienced a flare by the end of Part II.
Number of Participants Who Experienced a Disease Flare in Part II
时间窗: 32 weeks after study start
Disease flare is determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Disease Flare = the C-reactive protein and/or serum amyloid A (SAA) \> 30 mg/L and either a PGA \> minimal, or PGA equal to minimal and \> minimal SD.
次要结局
- Investigator's Clinical Assessment of Autoinflammatory Disease Activity & Participant's Assessment of Symptoms at End of Part II (After 24 Weeks of the Double-blind Part)(32 weeks after study start)
- Change in Inflammation Markers at the End of Part II (C-reactive Protein and/or Serum Amyloid A) (After 24 Weeks of the Double-blind Part) From Week 8.(Week 8 and Week 32)
- Pharmacokinetics (CLD (L/d))(48 weeks after study start)
- Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.(until Week 8)
- Number of Participants With Treatment Response in Part I (After 8 Weeks)(8 weeks after study start)
- Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.(32 weeks after study start)
- Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III.(48 weeks after study start)