A Two Part Randomized Cross-Over Trial to Evaluate the Pharmacokinetics, Efficacy, and Safety Profile of Plasma Protein-Free Recombinant FVIII Formulated With Sucrose (BAY81-8973) in Previously Treated Subjects With Severe Hemophilia A Under Prophylaxis Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 61
- 主要终点
- Part B - Annualized Number of Total Bleeds
研究概览
简要总结
The study will assess the pharmacokinetics (part A) safety, tolerability, and efficacy of prophylaxis treatment (2 to 3 times a week) (part B) with BAY81-8973 over a one year period (split into two six month treatment periods). The study will compare 2 different methods (assays) for measuring the amount of study drug, the chromogenic substrate assay per European Pharmacopeia (CS/EP) with the classical assay (Chromogenic Substrate Adjusted, CS/ADJ). During one six month period patients will receive the study drug where the dose has been measured using the" (CS/EP) and during the other six months period the dose will be measured based on the Chromogenic Substrate Adjusted assay CS/ADJ)
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
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, aged 12 to 65 years
- •Severe hemophilia A defined as < 1% FVIII:C
- •>/= 150 days of previous treatment with FVIII in lifetime
- •Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product
- •No history of or current FVIII inhibitors
排除标准
- •Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)
- •Low platelet count, abnormal kidney function, or liver disease
- •Received treatment with immune suppressing drugs within the last 3 months prior or requires treatment during the study. (Some drugs for hepatitis C, Human immunodeficiency virus (HIV), and steroids are allowed)
- •Receiving or has received other experimental drugs within 3 months prior to study entry
- •Allergy to Factor VIII or hamsters or mouse protein
研究组 & 干预措施
Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS
Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between
干预措施: Recombinant Factor VIII (BAY81-8973) (Biological)
Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)
Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between
干预措施: Recombinant Factor VIII (Kogenate FS, BAY14-2222) (Biological)
Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJ
Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months
干预措施: Recombinant Factor VIII (BAY81-8973) (Biological)
Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EP
Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia for 6 months
干预措施: Recombinant Factor VIII (BAY81-8973) (Biological)
Arm 5: Recombinant Factor VIII by CS/EP
Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks
干预措施: Recombinant Factor VIII (BAY81-8973) (Biological)
结局指标
主要结局
Part B - Annualized Number of Total Bleeds
时间窗: 12 months after randomization
The annualized number of bleeds experienced by participants
Part A - Area Under the Drug Concentration-time Curve (AUC)
时间窗: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.
To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.
Part A - Half-life (t 1/2)
时间窗: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.
To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.
次要结局
- Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)(15-30 minutes after the injection)
- Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period(6 months on each potency)
- Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed(6 months on each potency)
- Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire(Baseline and 12 months)
- Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire(Baseline and 12 months)
- Part C - Number of Participants With Incidence of Inhibitory Antibody Formation(before and 3 weeks after surgery)
- Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)(Up to 6 weeks after drug administration)
- Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)(Up to 12 months after drug administration)
- Part A - Number of Participants With Inhibitory Antibody Formation(Up to 6 weeks after first injection of study drug)
- Part B - Number of Participants With Incidence of Inhibitory Antibody Formation(Up to 12 months after drug administration)
- Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)(before and 3 weeks after surgery)
- Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)(Up to 12 months after drug administration)
- Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)(Up to 4 weeks after drug administration)
- Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)(before and 3 weeks after surgery)
- Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery(An average of 1 month after start of treatment)
- Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery(at the time of surgery)