An Open-label, Multicentre Study to Compare the Pharmacokinetics of Efanesoctocog Alfa Versus rFVIII Products, Damactocog Alfa Pegol or Turoctocog Alfa Pegol, After a Single Intravenous Dose of 50 IU/kg in a Fixed Sequence in Previously Treated Adults With Severe Haemophilia A.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 11
- 主要终点
- Half-life (t½) of efanesoctocog alfa, damactocog alfa pegol and turoctocog alfa pegol after a single i.v. injection
研究概览
简要总结
Sobi.BIVV001-003 is an open-label, 2-period, fixed sequence study for intra-participant comparison of the PK profiles of efanesoctocog alfa and the extended half-life rFVIII products damactocog alfa pegol or turoctocog alfa pegol after a single i.v. injection in previously treated males, 18-65 years of age, with severe haemophilia A.
Participants who are receiving treatment with damoctocog alfa pegol (n~12) or turoctocog alfa pegol (n~12) will be enrolled in the study. The study will start with a screening period (up to 28 days), including a wash-out period prior to start of the actual study period.
During the the first visit, a single dose of damactocog alfa pegol or turoctocog alfa pegol (corresponding to the participant's pre-study treatment) will be administered. A PK sampling period will follow over 7 visits. Following completion of the PK sampling of the original treatment regimen, the patients will be given a single dose of efanesoctocog alfa at visit 8, after which a new PK sampling period will follow (visit 8-15).
The primary objective for the study is to compare the half-life of efanesoctocog alfa with that of the two comparator drugs after a single iv. injections.
Secondary objectives include comparison of area under the curve for efanesoctocog alfa vs. the two comparator drugs, characterization of PK parameters for all three drugs as well as well as to evaluate safety and tolerability of a single iv. injection of efanesoctocog alfa.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant must be male, 18 to 65 years of age, inclusive, at the time of signing the informed consent form (ICF).
- •Severe haemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII activity, as documented in historical medical records from a clinical laboratory demonstrating <1% FVIII coagulant activity or a documented genotype known to produce severe haemophilia A.
- •Previous treatment for haemophilia A with any marketed recombinant and/or plasma derived FVIII for at least 150 exposure days.
- •Currently receiving treatment with damoctocog alfa pegol or turoctocog alfa pegol at Screening.
排除标准
- •Any history of a positive inhibitor test, defined as >0.6 Bethesda units (BU)/mL in at least two consecutive Bethesda inhibitor assays, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL. Family history of inhibitors will not exclude the participant.
- •Positive FVIII inhibitor result (assessed by central laboratory), defined as ≥0.6 BU/mL at Screening.
研究组 & 干预措施
Damactocog alfa pegol
Patients treated with damactocog alfa pegol at the time of screening will receive one single injection with 50 IU/kg at visit 1, then one single dose 50 IU/kg with efanesoctocog alfa at visit 8.
干预措施: Efanesoctocog alfa (Drug)
Turoctocog alfa pegol
Patients treated with turoctocog alfa pegol at the time of screening will receive one single injection with 50 IU/kg at visit 1, then one single dose 50 IU/kg with efanesoctocog alfa at visit 8.
干预措施: Efanesoctocog alfa (Drug)
结局指标
主要结局
Half-life (t½) of efanesoctocog alfa, damactocog alfa pegol and turoctocog alfa pegol after a single i.v. injection
时间窗: up to 7 days and 14 days after the administration of the respective drugs.
PK assessments will be based on FVIII activity levels determined by one-stage clotting assay
次要结局
- To compare the area under the curve zero to infinity (AUC∞) of efanesoctocog alfa with that of damoctocog alfa pegol and with that of turoctocog alfa pegol after a single i.v. injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize Cmax of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize clearance of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize volume of distribution of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize mean residence time of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize incremental recovery of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize time to specific plasma FVIII levels of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To characterize time spent in plasma FVIII:C normal range for efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection.(up to 7 days and 14 days after the administration of the respective drugs.)
- To evaluate the safety and tolerability of a single IV injection of efanesoctocog alfa.(From first dose of comparator to end of study, approximately 1 month.)