A Non-randomized, Open-label Study To Evaluate The Pharmacokinetics, Safety And Efficacy Of Refacto Af In Previously Treated Pediatric Subjects Less Than Twelve Years Of Age With Severe Hemophilia A (Fviii:c <1%).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 37
- 试验地点
- 34
- 主要终点
- Terminal Elimination Half Life of ReFacto AF (t1/2)
研究概览
简要总结
The study will be investigating pharmacokinetics, safety and efficacy in patients less than 12 years of age with severe hemophilia A that have been previously treated with Factor VIII products ( including blood products).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 11 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male subjects less than 12 years of age with a documented history of severe hemophilia A (FVIII:C less than 1%).
- •Subjects who are less than 6 years of age must have had at least 50 Exposure Days (EDs) to prior FVIII products (including blood products).
- •Subjects who are equal to or greater than 6 years of age must have had greater than 150 EDs to prior FVIII products (including blood products).
排除标准
- •For laboratory assessments, any measured Bethesda inhibitor titer equal to or greater than 0.6 BU, regardless of the laboratory normal range, or any Bethesda inhibitor titer greater than ULN for the testing laboratory at the time of screening.
- •Any other bleeding disorder in addition to hemophilia A.
- •Treatment with any investigational drug or device within 30 days before the time of signing the parental informed consent/assent form.
- •Major surgery planned to occur during the course of the study.
- •Regular (e.g., daily; every other day) use of agents or medications known to influence platelet function such as aspirin or certain nonsteroidal anti-inflammatory drugs (NSAIDS).
- •Regular, concomitant therapy with immunomodulating drugs (e.g., intravenous immunoglobulin [IVIG], routine systemic corticosteroids), or currently receiving immune tolerance induction (ITI) for inhibitor treatment.
- •The subject is receiving treatment for HIV or hepatitis infection (unless the subject is on a stable antiviral regimen [i.e., consistent treatment regimen for at least 3 months before the parental informed consent/assent form is signed]).
- •Platelet count less than 100,000/µL.
- •Prothrombin time (PT) equal to or greater than 1.25 x ULN, or international normalized ratio (INR) equal to or greater than 1.
- •Known hypersensitivity to hamster protein.
结局指标
主要结局
Terminal Elimination Half Life of ReFacto AF (t1/2)
时间窗: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
T1/2 was the time for the plasma concentration of drug to decrease by one-half of its original concentration.
Percentage of Participants With Clinically Significant Factor VIII Inhibitor Development
时间窗: Baseline up to Month 24
Clinically significant factor VIII (FVIII) inhibitors were defined as a central laboratory confirmed positive inhibitor of greater than or equal to (\>=) 0.6 Bethesda units (BU) using the Nijmegen modification of the Bethesda assay present at 2 consecutive blood draws within a 6-week interval and one of the following within 4 weeks before the initial or within 4 weeks following the second positive FVIII inhibitor sample collection: 1) the need for the participant to administer alternative hemostatic products in order to achieve sufficient efficacy, 2) \>=2 events indicating a decrease in the efficacy of the study treatment. Percentage of participants who developed clinically significant Factor VIII inhibitor after study drug administration were reported.
Incremental Recovery
时间窗: Days 1, 15, 50, Months 6, 18 and Final visit (up to Month 24)
Incremental recovery was the increase in circulating FVIII activity for every international unit (IU) of ReFacto AF administered per kilogram of body weight. It was measured in international units per deciliter (IU/dL) per international units per kilogram (IU/kg).
Clearance (CL)
时间窗: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
次要结局
- Total Factor VIII Consumption: All Participants(Baseline up to Month 24)
- Number of Participants Requiring Escalated Dose of Prescribed Regimen During the Treatment Period: All Participants(Baseline up to Month 24)
- Volume of Distribution at Steady State (Vss)(Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): All Participants(Baseline up to 30 days after last study visit (Month 25))
- Mean Annualized Bleeding Rates (ABRs): All Participants(Baseline up to Month 24)
- Response to First On-Demand Treatment for New Bleeds: All Participants(Baseline up to Month 24)
- Number of On-Demand ReFacto AF Infusions to Treat a New Bleed: All Participants(Baseline up to Month 24)
- Number of Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of ReFacto AF: All Participants(Baseline up to Month 24)
- Average Infusion Dose of ReFacto AF: All Participants(Baseline up to Month 24)
- Number of Less-Than-Expected-Therapeutic Effect (LETE) Bleeds in the On-Demand Setting: All Participants(Baseline up to Month 24)
- Number of Less-Than-Expected-Therapeutic Effect (LETE) Bleeds in the Prophylaxis Setting: All Participants(Baseline up to Month 24)
- Number of Occurrences of Less-Than-Expected-Therapeutic Effect (LETE) in the Low Recovery Setting: All Participants(Baseline up to Month 24)
- Plasma Concentration of Factor VIII at 0.5 Hour Post-dose (C0.5)(0.5 hour post-dose on Day 1)
- Area Under the Plasma Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)(Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1)
- Mean Residence Time (MRT) of ReFacto AF(Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1)
- Area Under the Plasma Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast)(Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1)