An Open-label, Multicenter Evaluation of Safety, Pharmacokinetics and Efficacy of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in the Prevention and Treatment of Bleeding Episodes in Pediatric Subjects With Hemophilia B
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Occurence of Factor IX (FIX) Inhibitor Development
研究概览
简要总结
The primary objective of the study is to evaluate the safety of Recombinant Human Coagulation Factor IX Fc Fusion Protein (rFIXFc) in previously treated pediatric subjects with hemophilia B. Secondary objectives of this study in this study population are as follows: to evaluate the efficacy of rFIXFc for prevention and treatment of bleeding episodes; to evaluate and assess the pharmacokinetics (PK) of rFIXFc; to evaluate rFIXFc consumption for prevention and treatment of bleeding episodes
详细描述
At the Baseline visit (28 ± 7 days prior to Day 1), participants receive a single IV injection of prestudy FIX over 10 (±5) minutes in the clinic under medical supervision at a dose of 50 IU/kg. A washout period with no FIX treatment is required prior to administration of prestudy FIX and prior to rFIXFc. A PK assessment is done with prestudy FIX and also done with rFIXFc on Day 1. After completing the PK assessments, participants begin weekly prophylactic treatment with rFIXFc for approximately 50 weeks, to obtain 50 EDs. One ED is defined as a 24-hour period in which a participant received 1 or more doses of rFIXFc, with the time of the first injection of rFIXFc defined as the start of the ED.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 11 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Severe hemophilia B defined as ≤ 2 IU/dl (≤ 2%) endogenous FIX
- •Male < 12 years and weight ≥ 13 kg
- •History of at least 50 documented prior exposure days to FIX
- •No history of, or currently detectable, inhibitor
排除标准
- •Other coagulation disorders in addition to Hemophilia B
- •History of anaphylaxis associated with any FIX or IV immunoglobulin administration
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
rFIXFc Prophylaxis
At Baseline and at Day 1, participants receive a single intravenous (IV) injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg will be administered in clinic as an IV injection.
Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.
干预措施: rFIXFc (Drug)
rFIXFc Prophylaxis
At Baseline and at Day 1, participants receive a single intravenous (IV) injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg will be administered in clinic as an IV injection.
Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.
干预措施: FIX (Drug)
结局指标
主要结局
Occurence of Factor IX (FIX) Inhibitor Development
时间窗: Up to 50 weeks +/- 7 days, or up to 50 EDs if reached prior to Week 50
An inhibitor test result ≥ 0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Incidences were summarized for any positive inhibitor for participants with ≥ 50 exposure days (EDs) to rFIXFc. In addition, the incidence for all participants, regardless of their EDs to rFIXFc, was also summarized. An exact 95% CI for the proportion of participants with a confirmed inhibitor was calculated using the Clopper-Pearson exact method for a binomial proportion.
次要结局
- Volume of Distribution at Steady State (Vss; One-stage aPTT Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)
- Maximum Plasma Activity (Cmax; One-stage Activated Partial Thromboplastin Time [aPTT] Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)
- Mean Residence Time (MRT; One-stage aPTT Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)
- Annualized Bleeding Rate(Up to 50 weeks +/- 7 days (efficacy period as defined in description))
- Annualized Joint Bleeding Rate (Spontaneous)(Up to 50 weeks +/- 7 days (efficacy period as defined in description))
- Annualized rFIXFc Consumption by Type of Injection(Up to 50 weeks +/- 7 days (efficacy period as defined in description))
- Number of Days From the Last Prophylaxis Injection to a Spontaneous Bleeding Episode(Up to 50 weeks +/- 7 days (efficacy period as defined in description))
- Participant Assessment of Response to Injections to Treat a Bleeding Episode(Up to 50 weeks +/- 7 days)
- Total Dose Required for Resolution of a Bleeding Episode(Up to 50 weeks +/- 7 days (efficacy period as defined in description))
- Terminal Half Life (t1/2; One-stage aPTT Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)
- Physician's Global Assessment of the Participant's Response to His rFIXFc Regimen(Up to 50 weeks +/- 7 days)
- Number of Injections Required for Resolution of a Bleeding Episode(Up to 50 weeks +/- 7 days (efficacy period as defined in description))
- Clearance (CL; One-stage aPTT Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)
- Dose Normalized Area Under the Curve (DNAUC; One-stage aPTT Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)
- Incremental Recovery (IR; One-stage aPTT Clotting Assay)(Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.)