A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants With Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 26
- 主要终点
- Participants With Thrombotic Microangiopathy (TMA) Response
研究概览
简要总结
This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 28 days of age up to < 18 years of age at the time of signing the informed consent.
- •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 ≥ 5 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 (VOD) 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 1 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.
- •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
Ravulizumab plus Best Supportive Care
Participants will receive ravulizumab plus Best Supportive Care as background therapy.
干预措施: Ravulizumab (Drug)
Ravulizumab plus Best Supportive Care
Participants will receive ravulizumab plus Best Supportive Care as background therapy.
干预措施: Best Supportive Care (Other)
结局指标
主要结局
Participants With Thrombotic Microangiopathy (TMA) Response
时间窗: Up to Week 26
The criteria for TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm\^3 or \>=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of lactate dehydrogenase (LDH, defined as LDH ≤ upper limit of normal \[ULN\]) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, with no criteria failures or more than 1 missed scheduled visit in between. Additionally, all intervals in which the criteria were met must overlap for at least 1 day.
次要结局
- Time to TMA Response During the 26-Week Treatment Period(Day 1 through Week 26)
- Participants With Hematologic Response(Up to Week 26)
- Time to Hematologic Response During the 26-Week Treatment Period(Day 1 through Week 26)
- Participants With Hemoglobin Response(Up to Week 26)
- Participants With Platelet Response(Up to Week 26)
- Participants With Partial TMA Response(Up to Week 26)
- Participants With Loss of TMA Response(Up to Week 26)
- Duration of TMA Response Through Week 52(Day 1 through Week 52)
- Participants With TMA Relapse(Up to Week 52)
- Overall Survival(Day 1 through Week 52)
- Non-relapse Mortality During the 52-Week Treatment Period(Day 1 through Week 52)