A Phase I Single Center, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Caplacizumab in Japanese and White Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- The number of treatment-emergent adverse events (Safety and Tolerability)
研究概览
简要总结
Primary objective:
To assess the safety and tolerability of single ascending intravenous (i.v.) doses, a single subcutaneous (s.c.) dose of caplacizumab (Part I), and multiple s.c. doses of caplacizumab (Part II) in Japanese subjects.
Secondary objectives:
- To compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles (total vWF:Ag concentration levels [vWF:Ag], coagulation factor VIII [FVIII:C], and ristocetin cofactor activity [RICO]) after single i.v. or s.c. administration of caplacizumab in Japanese and White subjects.
- To evaluate the immunogenicity of caplacizumab (anti-drug antibodies [ADA]) in Japanese subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between ≥18 kg/m² and <30 kg/m² at time of screening
- •Body weight between ≥45 kg and <100 kg
- •Baseline vWF:Ag between ≥60% and <170% (0.6-1.7 IU/mL)
排除标准
- •History of and/or any sign or symptom indicating current abnormal hemostasis or blood dyscrasia, including but not limited to thrombocytopenia, thrombocytopathy, thromboasthenia, hemophilia, von Willebrand's disease, vascular purpura, bleeding gums and/or frequent nose bleeding, easy/spontaneous bruises, meno- or metrorrhagia, history of gastrointestinal bleeding or excessive bleeding after minor injury such as shaving.
- •Family history of congenital vascular malformation (e.g., Marfan's Syndrome) and/or bleeding disorder (e.g., hemophilia, von Willebrand's disease, Christmas disease)
- •Any surgical intervention (including tooth extraction) or trauma within the 4 weeks preceding screening for the study or any planned surgical intervention during the participation in the study
- •Treatment with vitamin K, direct oral anticoagulant (DOAC), warfarin, high dose heparin within 2 weeks before screening
研究组 & 干预措施
Group 1: Japanese - Caplacizumab Dose 1 iv (SD)
Single dose (SD) of Caplacizumab Dose 1 administered intravenously (iv) to Japanese participants
干预措施: Caplacizumab Dose 1 iv (single-dose) (Biological)
Group 1: Japanese - Placebo iv (SD)
Single dose (SD) of Placebo administered intravenously (iv) to Japanese participants
干预措施: Placebo iv (single-dose) (Other)
Group 2: Japanese - Caplacizumab Dose 2 iv (SD)
Single dose (SD) of Caplacizumab Dose 2 administered intravenously (iv) to Japanese participants
干预措施: Caplacizumab Dose 2 iv (single-dose) (Biological)
Group 2: Japanese - Placebo iv (SD)
Single dose (SD) of Placebo administered intravenously (iv) to Japanese participants
干预措施: Placebo iv (single-dose) (Other)
Group 2: White - Caplacizumab Dose 2 iv (SD)
Single dose (SD) of Caplacizumab Dose 2 administered intravenously (iv) to White participants
干预措施: Caplacizumab Dose 2 iv (single-dose) (Biological)
Group 2: White - Placebo iv (SD)
Single dose (SD) of Placebo administered intravenously (iv) to White participants
干预措施: Placebo iv (single-dose) (Other)
Group 3: Japanese - Caplacizumab Dose 2 sc (SD)
Single dose (SD) of Caplacizumab Dose 2 administered subcutaneously (sc) to Japanese participants
干预措施: Caplacizumab Dose 2 sc (single-dose) (Biological)
Group 3: Japanese - Placebo sc (SD)
Single dose (SD) of Placebo administered subcutaneously (sc) to Japanese participants
干预措施: Placebo sc (single-dose) (Other)
Group 3: White - Caplacizumab Dose 2 sc (SD)
Single dose (SD) of Caplacizumab Dose 2 administered subcutaneously (sc) to White participants
干预措施: Caplacizumab Dose 2 sc (single-dose) (Biological)
Group 3: White - Placebo sc (SD)
Single dose (SD) Placebo administered subcutaneously (sc) to White participants
干预措施: Placebo sc (single-dose) (Other)
Group 4: Japanese - Caplacizumab Dose 2 sc (MD)
Multiple doses (MD) of Caplacizumab Dose 2 administered subcutaneously (sc) to Japanese participants
干预措施: Caplacizumab Dose 2 sc (multiple-dose) (Biological)
Group 4: Japanese - Placebo sc (MD)
Multiple doses (MD) of Placebo administered subcutaneously (sc) to Japanese participants
干预措施: Placebo sc (multiple-dose) (Other)
结局指标
主要结局
The number of treatment-emergent adverse events (Safety and Tolerability)
时间窗: From signing of informed consent form until Day 28 (single-dose part) or Day 34 (multiple dose part)
次要结局
- Pharmacokinetics: concentration of caplacizumab in plasma(From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part))
- Pharmacodynamics as measured by von Willebrand factor antigen in plasma(From screening to Day 6 (single dose part) or to Day 12 (multiple dose part))
- Pharmacodynamics as measured by Ristocetin cofactor activity in plasma(From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part))
- Pharmacokinetics: concentration of caplacizumab in urine(From Day 1 to Day 4 (single dose part) or to Day 8 (multiple dose part))
- Pharmacodynamics as measured by Factor VIII clotting activity in plasma(From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part))
- Immunogenicity as measured by the concentration of anti-caplacizumab antibodies in serum(From screening until Day 28 (single-dose part) or Day 34 (multiple dose part))