Multicenter, Randomized Phase III Inhibitor Prevention Trial, Comparing Eloctate vs. Emicizumab to Prevent Inhibitor Formation in Severe Hemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 3
- 主要终点
- Inhibitor Formation
研究概览
简要总结
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A.
详细描述
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which consecutive hemostatic agents will be compared using adaptive design to prevent inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. The INHIBIT Clinical Trials Platform includes two linked trials, the Inhibitor Prevention Trial (Prevention Trial) and the Inhibitor Eradication Trial (Eradication Trial) that will be conducted at up to 41 U.S. hemophilia treatment centers (HTCs) affiliated with universities. The Inhibitor Prevention Trial is a 48-week randomized phase III trial, in which 66 previously untreated patients (PUPs) with severe hemophilia A will be enrolled. Subjects will include children from 4 months of age up to 4 years of age who have not been previously treated with clotting factor. Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria will be randomized to preemptive weekly Eloctate (rFVIIIFc) vs. weekly Emicizumab (Hemlibra) to prevent inhibitor formation, defined as anti-FVIII >= 0.6 BU. Blood draws will be minimized to 6 timepoints, pre, 4, 12, 24, 36, and 48 weeks, and validated for small volumes, 3.8 cc (¾ tsp) each. The Inhibitor Prevention Trial is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained. (NB: The Inhibitor Prevention Trial (PRO19040140) is linked to the Inhibitor Eradication Trial (PRO19070080), as part of the INHIBIT Clinical Trials Platform, with both trials will be conducted efficiently in the same hemophilia treatment centers (HTCs), with the same MDs, coordinators, visit frequency, blood sampling, and assays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 4 Months 至 4 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male children >= 4 months and up to 4 years of age.
- •Severe hemophilia A (FVIII < 0.01 U/ml).
- •No evidence of an inhibitor i.e. anti-FVIII < 0.6 B.U.
- •No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.
排除标准
- •Acquired hemophilia or any bleeding disorder other than hemophilia A.
- •Treatment with clotting factor or emicizumab previously.
- •Use of an experimental drug(s).
- •Surgery anticipated in the next 48 weeks.
- •Life expectancy less than 5 years.
- •Parent/caretaker unable or unwilling to keep a personal diary of bleeding frequency and study drug treatment, make monthly visits and blood draws at weeks 4, 12, 24, 36, and
- •Other illness, condition or reason in the opinion of the investigator that would make the patient unsuitable for the trial.
研究组 & 干预措施
Eloctate
Arm A: Eloctate 65 IU/kg will be administered weekly by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued up to 48 weeks.
干预措施: Eloctate Injectable Product (Drug)
Emicizumab
Arm B: Emicizumab 1.5 mg/kg will be administered weekly by subcutaneous injection (following 3 mg/kg/wk x4 induction) in previously untreated children with severe hemophilia A beginning before the first bleed and continue up to 48 weeks.
干预措施: Emicizumab Injection [Hemlibra] (Drug)
结局指标
主要结局
Inhibitor Formation
时间窗: 48 weeks
The proportion developing anti-FVIII inhibitors.
次要结局
- FVIII Mutation(48 weeks)
- Bleeding Events(48 weeks)
- FVIII Trough Level(48 weeks)
- Human Leukocyte Antigen (HLA) Haplotype(48 weeks)
- Number of FVIII Exposures(48 weeks)
研究者
Margaret Ragni
Professor of Medicine and Clinical and Translational Research
University of Pittsburgh