A Phase 3, Open-label, Multicenter, Pharmacokinetics, Efficacy, and Safety Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Chinese Subjects With Hemophilia B
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 23
- 试验地点
- 14
- 主要终点
- Number of subjects who develop an inhibitor to FIX
研究概览
简要总结
This study will investigate the pharmacokinetics (PK), efficacy, and safety of rIX-FP for the routine prophylaxis of bleeding episodes in male Chinese previously treated patients (PTPs) with hemophilia B (FIX activity of ≤ 2%). In addition to the scheduled rIX-FP prophylaxis regimen, subjects may also receive rIX-FP episodic (on-demand) treatment for breakthrough bleeding episodes and rIX-FP for the prophylaxis and treatment of bleeding in emergency surgical procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male Chinese subjects aged ≤ 70 years
- •Subjects with documented severe or moderately severe hemophilia B (FIX activity of ≤ 2%)
- •Subjects have received FIX products for ≥ 150 exposure days (EDs) (subjects aged ≥ 6 years) or ≥ 50 EDs (subjects aged < 6 years)
- •Subjects have no confirmed prior history of FIX inhibitor formation
排除标准
- •Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein.
- •Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
- •Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
- •Currently receiving a long-acting recombinant FIX treatment such as coagulation factor IX (recombinant), Fc fusion protein (Alprolix®).
- •Use of traditional or herbal Chinese medicine(s) with an impact on hemophilia, including coagulation, within 28 days before Day 1 and / or refusal to abstain from these during the study until the end of the subject's participation in the study.
研究组 & 干预措施
rIX-FP
Subjects will receive rIX-FP as an intravenous (IV) infusion for a minimum of 50 exposure days (EDs)
干预措施: Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) (Biological)
结局指标
主要结局
Number of subjects who develop an inhibitor to FIX
时间窗: Up to 18 months after rIX-FP infusion
Maximum plasma concentration (Cmax)
时间窗: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Terminal elimination half-life (t1/2) of rIX-FP
时间窗: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Area under the concentration-time curve (AUC)
时间窗: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf).
Clearance (Cl) of rIX-FP
时间窗: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Incremental recovery (IR) (plasma FIX activity)
时间窗: Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1
Annualized spontaneous bleeding rate (AsBR)
时间窗: Up to 18 months
AsBR for treated bleeding episodes, by prophylaxis regimen and overall
次要结局
- Change in target joints(At baseline and up to 18 months after rIX-FP infusion)
- Consumption of rIX-FP - IU/kg per subject per year(Up to 18 months after rIX-FP infusion)
- Area under the first moment versus time curve extrapolated to infinity (AUMC0-∞)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Mean residence time (MRT)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Annualized joint bleeding rate (AjBR)(Up to 18 months after rIX-FP infusion)
- Apparent volume of distribution during the terminal phase (Vz)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Incremental recovery (IR) (plasma FIX activity) - Repeat PK(Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26)
- Consumption of rIX-FP - number of rIX-FP infusions (doses)(Up to 18 months after rIX-FP infusion)
- Time to reach Cmax (Tmax)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Maximum plasma concentration (Cmax) - Repeat PK(Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26)
- Clinical evaluation of hemostatic efficacy for major bleeding episodes(Up to 18 months after rIX-FP infusion)
- Apparent volume of distribution at steady-state (Vss)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Elimination rate constant (λz)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Area under the concentration-time curve (AUC) - Repeat PK(Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26)
- Clearance (Cl) of rIX-FP - Repeat PK(Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26)
- Percentage of bleeding episodes requiring rIX-FP to achieve hemostasis(Up to 18 months after rIX-FP infusion)
- Percentage of area under the concentration-time curve extrapolated (%AUCExt)(Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK))
- Terminal elimination half-life (t1/2) of rIX-FP - Repeat PK(Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26)
- Number of bleeding episodes requiring rIX-FP to achieve hemostasis(Up to 18 months after rIX-FP infusion)
- Number of subjects who develop antibodies against rIX-FP(Before, and up to 18 months after, rIX-FP infusion)
- The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP(Up to 18 months after rIX-FP infusion)
- Annualized bleeding rate (ABR)(Up to 18 months after rIX-FP infusion)
- Consumption of rIX-FP - IU/kg per subject per month(Up to 18 months after rIX-FP infusion)
- The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP(Up to 18 months after rIX-FP infusion)
- Number of subjects who develop antibodies against Chinese hamster ovary host cell protein(Before, and up to 18 months after, rIX-FP infusion)