International, Multicenter, Double Blind, Placebo-controlled, Randomized Clinical Study of Efficacy and Safety of RPH-104 for Resolution and Prevention of Recurring Attacks in Adult Subjects With Familial Mediterranean Fever With Resistance to or Intolerance of Colchicine
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 84
- 试验地点
- 14
- 主要终点
- Proportion of subjects with complete response during 16 week therapy with RPH-104 vs. placebo in FMF subjects with colchicine inefficacy or intolerance.
研究概览
简要总结
Study purpose is an evaluation of efficacy and safety of RPH-104 in the population of subjects with Familial Mediterranean Fever (FMF) with colchicine resistance or intolerance(i.e. colchicine resistant (crFMF).. Primary objective is to determine proportion of subjects with complete response to treatment with RPH-104 compared to placebo among FMF subjects with colchicine resistance or intolerance.
详细描述
The study is supposed to enroll (randomize) (n= not less than 28, not less than 14 per group), so that not less than 24 to complete study in full (including all the treatment period visits and follow-up period visits - Visit 11 for patients who agreed to participate in the Open-label extension (OLE) study; Visit 11 and Visit 12 for those who do not wish to participate in the OLE study; given potential withdrawal at screening the number of screened subjects (signed Informed Consent Form (ICF) is planned to be up to 84.
The study will consists of three following periods:
- Screening period (up to 12 weeks); Throughout the screening the subjects will be monitored to identify "marker" attacks and verify the subject eligibility. The subjects having an attack during screening period and meeting inclusion/exclusion criteria will be enrolled into treatment period.
- Double-blind randomized placebo-controlled treatment period (16 weeks);
The subjects enrolled will be randomized to one of the treatment groups in 1:1 ratio:
- RPH-104 group to receive subcutaneous (SC) injections according to the following regimen: 160 mg on Day 0, 80 mg on Day 7, Day 14 and once every 2 weeks (q2w) thereafter;
- placebo group to receive matching SC injections on Day 0, Day 7, Day 14 and q2w thereafter.
Efficacy assessment will be performed at Visit 2 and Visit 3, and subsequently every 2 weeks up to Visit 10 inclusive; safety assessment will be performed throughout the study (Visit 1 - Visit 12). In a case of adverse event (AE) development (or other safety reasons), additional unscheduled safety visits could be performed throughout the study. Starting from Visit 2, additional unscheduled visits due to suspected development of FMF attack could be performed. In a case of a recurrent attack, the patient should come to the study site within 2 days from the attack onset for the attack registration.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 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
RPH-104
Test product group receiving RPH-104 subcutaneous (s.c.) injections:160 mg on Day 0, 80 mg on Day 7, Day 14 and every 2 weeks (q2w) thereafter.
In case "marker" attack does not resolve at Visit 2 - the treatment group will be unblinded: patients will receive planned RPH-104 80 mg administration.
In case of a new attack on further days of treatment period until Visit 10 inclusive - the treatment group will be unblinded: the dose of RPH-104 could be escalated to 160 mg q2w; The patients already receiving RPH-104 160 mg q2w will continue to receive RPH-104 at this dose. Further dose escalation is forbidden.
干预措施: RPH-104 (Biological)
Placebo
Placebo group receiving the equivalent placebo dose also as s.c. injections on Day 0, Day 7, Day 14 and q2w thereafter.
In case the "marker" attack does not resolve at Visit 2 - the treatment group will be unblinded: patients will be switched to active treatment with RPH-104 in SC injections at a dose of 160 mg followed by administration of 80 mg in 7 days at the Attack + 7 days Visit, and 80 mg at the next Visits.
In a case of a new attack the patients switching from placebo and receiving RPH-104 at 80 mg dose could be escalated to RPH-104 160 mg q2w; Further dose escalation is forbidden.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of subjects with complete response during 16 week therapy with RPH-104 vs. placebo in FMF subjects with colchicine inefficacy or intolerance.
时间窗: Up to 16 weeks
Complete response defined as resolution of "marker" attack by Visit 2 (Day 7) and lack of recurrent attacks during the treatment period up to Visit 10 (Day 112). Criteria of resolution of a "marker" FMF attack include simultaneous clinical and laboratory signs of the attack resolution: * Physician Global Assessment (PGA) score \< 2 (i.e. minimum or complete lack of clinical signs and symptoms) AND * C-reactive protein (CRP) level ≤ 10 mg/L OR CRP reduction by ≥ 70% compared to baseline defined at enrollment to treatment period (Visit 1). Criteria of a recurrent FMF attack development after resolution of "marker" attack include simultaneous development of clinical and laboratory signs of the attack: * PGA score ≥ 2 assuming mild, moderate or severe disease activity (i.e. clinical signs), AND * CRP level ≥ 30 mg/L (serological signs). PGA is a 5-point scale: from 0 = no disease-related clinical signs and symptoms to 4 = severe clinical signs and symptoms of the disease.
次要结局
- Time to the development of a recurrent FMF attack in patients with resolved "marker" attacks(from Day 7 to the development of a recurrent FMF attack, up to 16 weeks)
- Proportion of subjects with Physician Global Assessment (PGA) score < 2 during the study(Up to 16 weeks)
- Proportion of subjects with partial response to treatment(Up to 16 weeks)
- Proportion of subjects with serological remission(Up to 16 weeks)
- Proportion of subjects with normalized Serum Amyloid A (SAA) level(Up to 16 weeks)
- Proportion of subjects escalated to RPH-104 160 mg q2w dose(Up to 16 weeks)
- Proportion of subjects receiving additional symptomatic therapy with Nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol or glucocorticoids due to FMF(Up to 16 weeks)
- Change in inflammation parameters vs. baseline (CRP)(From baseline (Day 0) up to 18 weeks)
- Change in inflammation parameters vs. baseline (SAA)(From baseline (Day 0) up to 18 weeks)
- PGA score change compared to baseline(From baseline (Day 0) up to 18 weeks)
- Changes in patients' quality of life during the treatment period with RPH-104(From baseline (Day 0) up to 18 weeks)