A Phase II, Multicentre, Double-blinded, Randomised, Cross-over Study to Evaluate Efficacy, Safety and Pharmacokinetics of Biostate® in Subjects With Haemophilia A.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 81
- 试验地点
- 14
- 主要终点
- Number of treatments/units required to resolve any bleeding event
研究概览
简要总结
The aim of this study are to
- assess the efficacy of Biostate® [Study Product (SP)] in subjects with Haemophilia A
- compare the pharmacokinetics of Biostate® [SP] with the previously marketed product Biostate® (here referred to as Biostate® [Reference Product (RP)]).
This study is divided into 3 parts:
Part 1: Cross-over pharmacokinetic (PK) component. PK subjects will be randomised to determine the order in which they receive the two study products. This part of the study is double-blinded.
Part 2: Efficacy component. All subjects will receive Biostate® [SP] as required to manage their haemophilia condition for an estimated period of 6 months (or minimum of 50 exposure days) to assess efficacy and safety of the product. This part of the study is open-label.
Part 3: Repeat pharmacokinetic assessment. Subjects who participated in Part 1 (PK component) will undergo a repeat PK assessment on Day 180 following administration of Biostate® [SP].
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with Haemophilia A with ≤ 1% Factor VIII (FVIII) levels in the absence of factor replacement
- •Evidence of vaccination against hepatitis A and B (or presence of antibodies against hepatitis A and B due to either a previous infection or prior immunisation) within 10 years prior to Day 1 documented in the medical notes
- •At least 150 days of prior exposure to a FVIII replacement product
- •Written informed consent given
排除标准
- •(for participation in the pharmacokinetic (PK) component):
- •Active bleeding
- •Body weight > 100 kg
- •Exclusion Criteria (for all subjects):
- •Receipt of an infusion of any FVIII product, cryoprecipitate, whole blood, plasma, or desmopressin acetate (DDAVP) in the 4 days prior to Day 1
- •Known history of FVIII inhibitors, or FVIII inhibitor level > 0.6 Bethesda Units (BU) at screening
- •Receipt of aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within 7 days of administration of study product.
- •CD4 lymphocytes < 200/µL. Subjects wo are HIV-1 positive may be considered for the study if viral load ≤ 200 particles/µL at screening and all other eligibility criteria are met.
- •Impaired liver function ie. bilirubin >1.5 x upper limit of normal (ULN) and/or AST/ALT > 2.5 x ULN at screening.
- •Acute or chronic medical condition, other than haemophilia A, which may, in the opinion of the Investigator, affect the conduct of the study
- •von Willebrand Disease (VWD) with Von Willebrand Factor:Ristocetin Cofactor (vWF:RCo) level < 50 IU/dL at screening
- •Evidence or a history (within the previous 12 months) of abuse of any drug substance, licit or illicit
- •Known or suspected hypersensitivity or previous evidence of severe side effects to Biostate®, FVIII concentrates or human albumin
- •Participation in a clinical study or use of an investigational compound (e.g. a new chemical entity not approved for clinical use) in the 3 months preceding the first day of study drug administration, or plans to enter such a study during the study period
- •Not willing and/or not able to comply with study requirements
研究组 & 干预措施
PK Biostate® [SP]
Part 1: PK subjects are randomized to receive Biostate® [SP] either on Day 1 or Day 8.
Part 3: All PK subjects receive Biostate® [SP] on Day 180.
干预措施: Biostate® [SP] (Biological)
PK Biostate® [RP]
Part 1: PK subjects are randomized to receive Biostate® [RP] either on Day 1 or Day 8.
干预措施: Biostate® [RP] (Biological)
Efficacy
Part 2: This arm includes all subjects during the efficacy component of the study.
干预措施: Biostate® [SP] (Biological)
结局指标
主要结局
Number of treatments/units required to resolve any bleeding event
时间窗: From Day 1 until final study visit
Assessment of blood loss during any surgical procedure
时间窗: From Day 1 until final study visit
FVIII concentrate usage (number of infusions, IU/kg per event, per month, and per year)
时间窗: From Day 1 until final study visit
Pharmacokinetics of FVIII activity
时间窗: Up to 48 hours following infusions (Part 1 and Part 3 only)
Haemostatic efficacy
时间窗: Monthly, until final study visit
次要结局
- The nature, frequency and incidence of adverse events(From Day 1 until final study visit)
- Development of FVIII inhibitors(From Day 1 until final study visit)