R34 Pilot Feasibility Randomized, Noninferiority, Cross-Over Trial of Once-Weekly vs. Thrice-Weekly Prophylaxis With Recombinant Factor VIII in Adults With Severe Hemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 6
- 主要终点
- Number of Bleeds
研究概览
简要总结
The purpose of this pilot R34 trial is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis comparing once weekly with thrice-weekly recombinant factor VIII. Efficacy will measured by bleeding frequency, factor usage, joint range of motion, cost, quality-of-life, F.VIII level, and inter-dose hypocoagulability by thrombin generation. Safety will be measured by inhibitor formation and bleeding events unresponsive to up to two rescue doses.
详细描述
The purpose of this 52-week pilot R34 randomized, open-label, non-inferiority, cross-over study is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis. The primary efficacy endpoint will be bleeding frequency. Secondary endpoints will include factor usage, joint range of motion, cost, quality-of-life, and inter-dose hypocoagulability by thrombin generation time and F.VIII activity will also be determined. Safety will be measured by the frequency of bleeding unresponsive to up to two rescue treatments. Inhibitor formation by anti-F.VIII Bethesda assay, and clinical frequency of thrombosis and allergic reactions will also be assessed. Subject acceptance and adherence to the treatment interventions will be determined; and web-based data entry of case report forms, digital range-of-motion images, and quality-of-life instrument will be implemented. The relation of bleeding frequency to relative inter-dose hypocoagulability, will be assessed by inter-dose thrombin generation time (TGT), endogenous thrombin potential (ETP), and factor VIII levels. Optimal blood sample collection and shipping methods will be determined. For all tests, we will estimate and determine completeness and congruency, in order to determine adjustments or revisions required before initiating a large phase III Randomized clinical trial. All testing will be exploratory, so that we may determine if the test, approach are realistic, and to estimate standard deviations for future power analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adult males 18 years or older
- •Severe hemophilia A (F.VIII < 0.01 U/ml)
- •At least 150 exposure days to F.VIII products
- •No detectable inhibitor
- •No history of allergic reaction
- •Platelets at least 150,000/ul
- •If HIV(+), CD4 at least 200/ul, HIV-VL <48 copies/ml,and cART compliant
- •If HCV(+), no splenomegaly,varices,GI bleed,ascites,edema,encephalopathy
- •Willingness to comply with cross-over design, randomization schema
- •Willingness to keep a personal diary of bleeding frequency and factor use
- •Willingness to make every 3 month visits, coagulation testing at wks 2, 28
排除标准
- •Acquired hemophilia
- •Any bleeding disorder other than hemophilia A
- •Presence of an inhibitor to factor VIII
- •Historic platelet count < 100,000
- •Use of experimental drugs
- •Surgery anticipate in the next 52 weeks
- •Symptomatic HCV(splenomegaly,varices,GI bleed,ascites,edema,encephalopathy)
- •Symptomatic HIV(CD4<200/ul or HIV VL 48 or more copy/ml,cART noncompliant)
- •Life expectancy less than 5 years
- •Investigational drug or study within 4 weeks prior to study
- •Inability to comply with study requirements
研究组 & 干预措施
Arm A
The intervention for Arm A is 40 IU/kg recombinant factor VIII (rFVIII) by once-weekly intravenous injection for 26 weeks.
Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given thrice-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds.
干预措施: rF.VIII (Drug)
Arm B
The intervention for Arm B is 40 IU/kg recombinant factor VIII (rFVIII) by thrice-weekly intravenous injection for 26 weeks.
Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given once-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds
干预措施: rF.VIII (Drug)
结局指标
主要结局
Number of Bleeds
时间窗: Weeks 26 (first intervention) and 52 (second intervention)
The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant.
次要结局
- Inter-dose Hypocoagulability by Thrombin Generation(The time frame is 52 weeks per subject.)
- F.VIII Activity(The time frame is 52 weeks per subject.)
研究者
Margaret Ragni
Laurel Yasko
University of Pittsburgh