A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 84
- 试验地点
- 37
- 主要终点
- Treatment Success
研究概览
简要总结
This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects ≥ 6 to < 12 years of age and at least 25 subjects < 6 years of age who have undergone > 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.
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
- •Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records,
- •Males < 12 years of age,
- •Subjects who have received > 50 EDs with a FVIII product,
- •Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part
- •Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements.
排除标准
- •Any history of or current FVIII inhibitors
- •Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration,
- •Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain,
- •Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein,
- •Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment,
- •Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values >5 times (x) the upper limit of normal (ULN) at Screening,
- •Subjects with serum creatinine values >2 x ULN at Screening,
- •Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1,
- •Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration.
研究组 & 干预措施
rVIII-SingleChain
Subjects will be assigned to either an on-demand or prophylaxis regimen and will receive rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen will be treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode is based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects will receive a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
干预措施: rVIII-SingleChain (Biological)
结局指标
主要结局
Treatment Success
时间窗: Up to 1 year
Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.
次要结局
- Annualized Bleeding Rate(Up to 1 year)
- Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year(Up to 1 year)
- Incremental Recovery(At 1 hour after the start of infusion)
- Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month(Up to 1 year)
- Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event(Up to 1 year)
- Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month(Up to 1 year)
- Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.(Up to 1 year)
- Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year(Up to 1 year)
- Half-life (t1/2) of rVIII-SingleChain(Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.)
- Number of Subjects With Inhibitor Formation to rVIII-SingleChain(At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).)
- Area Under the Concentration Curve (AUC)(Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.)
- Clearance (Cl) of rVIII-SingleChain(Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.)