A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Ravulizumab in Adult and Adolescent Participants Who Have Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplant (HSCT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 67
- 主要终点
- Event Free Survival
研究概览
简要总结
This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab in adult and adolescent participants with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label, single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be randomized to receive either blinded ravulizumab plus best supportive care or matching placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1, and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-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
- 12 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •12 years of age or older at time of consent/assent.
- •Received HSCT within the past 12 months.
- •Diagnosis of TMA that persists for at least 72 hours after initial management of any triggering agent/condition.
- •A TMA diagnosis based on meeting the laboratory-based criteria during the Screening Period and/or ≤14 days prior to the Screening Period.
- •Body weight ≥ 30 kilograms at Screening or ≤7 days prior to the start of the Screening Period (date of consent).
- •Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.
- •Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis. Participants <18 years of age must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible.
- •Participants or their legally authorized representative must be capable of giving signed informed consent or assent.
排除标准
- •Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency
- •Known Shiga toxin-related hemolytic uremic syndrome as demonstrated by positive test.
- •Positive direct Coombs test indicative of a clinically significant immune-mediated hemolysis not due to TMA.
- •Clinical diagnosis of disseminated intravascular coagulation (DIC).
- •Known bone marrow/graft failure for the current HSCT.
- •Diagnosis of veno-occlusive disease which is unresolved at the time of Screening.
- •Human immunodeficiency virus (HIV) infection.
- •Unresolved meningococcal disease.
- •Presence of sepsis requiring vasopressor support.
- •Pregnancy or breastfeeding.
- •Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
- •Any ongoing or history of medical or psychological conditions unrelated to HSCT-TMA that could increase the risk to the participant or confound the outcome of the study.
- •Respiratory failure requiring mechanical ventilation.
- •Acute and/or chronic heart failure with an ejection fraction ≤ 40%.
- •Previously or currently treated with a complement inhibitor.
- •Participation in an interventional treatment study of any therapy for TMA.
研究组 & 干预措施
Placebo
In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.
干预措施: Best supportive care (Other)
Ravulizumab
In Stage 1, all participants will receive open-label ravulizumab plus Best Supportive Care (BSC).
In Stage 2, participants will receive blinded ravulizumab plus Best Supportive Care (BSC).
干预措施: Best supportive care (Other)
Placebo
In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.
干预措施: Placebo (Other)
Ravulizumab
In Stage 1, all participants will receive open-label ravulizumab plus Best Supportive Care (BSC).
In Stage 2, participants will receive blinded ravulizumab plus Best Supportive Care (BSC).
干预措施: Ravulizumab (Biological)
结局指标
主要结局
Event Free Survival
时间窗: 26 weeks (treatment period)
Event free survival during the 26 weeks treatment period defined as the time from randomization until the first of the two following events: death and clinical worsening.
次要结局
- Duration of TMA Response(26 weeks (treatment period) and 52 weeks)
- Hematologic Response(26 weeks (treatment period))
- TMA response and time to response for each individual component of TMA(26 weeks (treatment period))
- Partial Response(26 weeks (treatment period))
- Loss of TMA Response(26 weeks (treatment period))
- Change from Baseline in eGFR(26 weeks (treatment period) and 52 weeks)
- Time to Hematologic Response(26 weeks (treatment period))
- Time To TMA Response(26 weeks (treatment period))
- Modified TMA Response(26 weeks (treatment period))
- TMA Relapse(Follow-up Period)
- Overall Survival(Day 100, 26 weeks (treatment period), and 52 weeks)
- Non-relapse Mortality(Day 100, 26 weeks (treatment period), and 52 weeks)
- Hemoglobin Response(26 weeks (treatment period))
- Changes from Baseline in Haptoglobin, Platelets, LDH, and Hemoglobin(26 weeks (treatment period) and 52 weeks)
- Change from baseline in TMA-associated organ dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system(26 weeks (treatment period) and 52 weeks)
- Platelet Response(26 weeks (treatment period))