Phase 1 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Ascending Doses of Subcutaneous Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 8
- 主要终点
- Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last
研究概览
简要总结
This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, pharmacodynamics, and safety of a single IV dose of MarzAA followed by ascending single SC doses of MarzAA in adult subjects with moderate or severe Hemophilia A or B, with or without an inhibitor.
详细描述
This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, pharmacodynamics, and safety of a single IV dose of MarzAA followed by ascending single SC doses of MarzAA in adult subjects with moderate or severe Hemophilia A or B, with or without an inhibitor. The study will enroll at least 8 adult male subjects with moderate or severe Hemophilia A or B with or without an inhibitor, in each dosing stage. Each subject will receive escalating doses of MarzAA for each stage of the study (except for Stage 5, where subjects receive the same dose as in Stage 4 split between two anatomical sites).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Moderate or severe congenital Hemophilia A or B, with or without an inhibitor
- •Male, age 18 or older
- •Affirmation of informed consent with signature confirmation before any trial related activities
排除标准
- •Inability to discontinue and washout prophylaxis treatment 72 hours prior to dosing.
- •Previous participation in a trial involving SC Administration of rFVIIa or any trial using a modified amino-acid sequence FVIIa
- •Known positive antibody to FVII or FVIIa detected by central laboratory at screening
- •Have a coagulation disorder other than hemophilia A or B, with or without an inhibitor
- •Significant contraindication to participate
结局指标
主要结局
Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last
时间窗: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.
Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups
Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose
时间窗: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.
Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups
次要结局
- Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Comparative MarzAA Activity of Intravenous and Subcutaneous - CL(Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.)
- Change in Thrombogenicity Parameter - Fibrinogen(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Change in Thrombogenicity Parameter - Thrombin/Antithrombin(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Occurrence of an Antibody Response to MarzAA(From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing.)
- Change in Coagulation Parameters - Prothrombin Time (PT)(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).)
- Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Change in Thrombogenicity Parameter - D-Dimer(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
- Occurrence of Clinical Thrombotic Event(From the date of first dose of MarzAA until date of first occurrence of clinical event, assessed up to End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing.)