A Patient-Blinded, Randomized, Comparative, Multicenter, Crossover, (Liposome) Dose Finding Study of the Efficacy of Human Recombinant Factor VIII (Kogenate FS) Reconstituted in Pegylated Liposomes.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 6
- 主要终点
- The primary efficacy parameter is the number of bleeding free days (without a bleeding/treatment) between a randomized prophylactic infusion and following on demand injection.
研究概览
简要总结
Primary efficacy endpoint: To study whether there is a difference in the length of the bleeding free periods between infusion of FVIII that is reconstituted with 22.1, 12.6, or 4.2 mg of pegylated liposomes per kg bwt compared with standard formulation.
Safety endpoint: To study the safety and tolerability of Kogenate FS reconstituted with Pegylated liposomes
详细描述
Each subject will receive treatment for three bleeding episodes ("wash-in", on demand injections) followed by a minimum 4 day wash-out. Following this each subject will be randomized to a specific treatment order. Each order consists of four identical blocks. In each block the following three injections will be given: 1 One prophylactic treatment (randomized solution for dissolution) 2 and 3. Two standard on-demand treatments for a spontaneous bleeding episode (standard Kogenate FS). Each block will be followed by a four day wash-out. In total each subject should receive 3+4x3=15 injections. It is estimated that each subject will be in the study for about 4 months. A treatment for a spontaneous bleeding episode may require more than one infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Between 18 and 60 years of age
- •Severe haemophilia A (≤ 1% of baseline Factor VIII activity)
- •At least 250 treatment cumulative exposure-days (CEDs) to previous products
- •At least 25 cumulative exposure-days (CEDs) to previous products during one year prior to study start
- •If HIV positive, CD4 lymphocytes ≥ 400/µl
- •Subjects on demand treatment, and with a minimum bleeding/treatment pattern of a four episodes per month, evenly distributed within each month, during the three month preceding study start
- •Subjects who have given their written informed consent.
排除标准
- •Inhibitors or history of inhibitors
- •History of adverse reactions related to Factor VIII
- •Platelet count <90,000 /µl
- •Subjects on prophylaxis treatment
- •Subjects with concomitant debilitating disease (e.g. cancer, non-controlled diabetes, heart insufficiency, renal failure)
- •Subjects with known sensitivity to blood products
- •Subjects who have participated in another Ethical Committee approved Clinical Trial (including medical device studies) within the past 30 days
- •Subjects with a weight over 86 kg or below 50 kg
- •Subjects who do not understand or are not willing to comply with the requirement of the study protocol
- •Subjects who cannot differentiate a bleeding episode from other causes of joint pain
结局指标
主要结局
The primary efficacy parameter is the number of bleeding free days (without a bleeding/treatment) between a randomized prophylactic infusion and following on demand injection.
时间窗: Bleeding free time following four single doses will be studies
次要结局
- In vivo recovery (IVR).(IVR will be performed at the first and last dose.)