Multi-center, Randomized, Open-label, Parallel-Arm, Single-dose, Pharmacokinetic Study of rVIIa-FP (CSL689) in Subjects With Congenital Factor VII Deficiency
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 9
- 试验地点
- 4
- 主要终点
- Terminal half-life of plasma FVIIa activity
研究概览
简要总结
The purpose of this study is to investigate the pharmacokinetics (PK) and safety of rVIIa-FP (CSL689) in a total of 10 to 16 male or female adults with inherited coagulation factor VII (FVII) deficiency. Subjects will receive a single dose of their routine FVII replacement product (ie, either recombinant activated coagulation FVII [rFVIIa, eptacog alfa (activated)] or plasma-derived FVII [pdFVII]) as a comparator, and will then be randomly assigned to a single low dose or a single high dose of the study product CSL689 (8 subjects per CSL689 dose level). Serial blood samples for PK analysis will be taken up to 24 hours after the eptacog alfa (activated) or pdFVII injection, and up to 48 hours after the CSL689 injection. Subject safety will be routinely monitored throughout the study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Proven congenital FVII deficiency.
- •Age ≥ 18 years.
- •FVII level < 2% of normal levels.
- •Minimum of 50 previous exposure days to pdFVII (including prothrombin complex concentrates [PCCs]) or rFVIIa.
排除标准
- •History of, or risk factors for, thromboembolic events, including known deep vein thrombosis.
- •Inhibitor to FVII or rFVIIa, current or historic.
- •Known or suspected hypersensitivity to hamster protein, to CSL689, or to any excipient of CSL
- •Known or suspected allergy to rFVIIa or hamster protein.
- •Major surgery within 1 month before screening.
- •Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke).
- •Human immunodeficiency virus (HIV)-positive subjects with cluster of differentiation 4 (CD4)+ lymphocyte count of < 200/µL at screening.
- •Use of an investigational agent within 30 days before the study.
- •Use of concomitant therapy not permitted during the study (ie, other platelet inhibitors, desmopressin, fibrinolysis inhibitors, except if used as local treatment [eg, for oral bleeds])
结局指标
主要结局
Terminal half-life of plasma FVIIa activity
时间窗: Up to 48 hours after CSL689 injection
Maximum observed plasma FVIIa activity
时间窗: Before injection and at up to 9 time points until 48 hours after injection
Area under the curve (AUC0-t)
时间窗: Before injection and at up to 9 time points until 48 hours after injection
Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity
次要结局
- Total clearance(Before injection and at up to 9 time points until 48 hours after injection)
- Volume of distribution of the terminal phase(Before injection and at up to 9 time points until 48 hours after injection)
- AUC(0-inf)(Before injection and at up to 9 time points until 48 hours after injection)
- Incremental recovery(Before injection and at up to 9 time points until 48 hours after injection)
- Number of subjects with antibodies against Chinese hamster ovary protein and FVII(Up to 30 days after CSL689 injection)
- Number of subjects with inhibitors against FVII(Up to 30 days after CSL689 injection)
- Time of occurrence of maximum observed plasma FVIIa activity(Before injection and at up to 9 time points until 48 hours after injection)