Randomized, Open-label, Double Cycle, Crossover, Pharmacokinetics Study of Recombinant Coagulation Factor VIII Injection Versus Xyntha® in Subjects With Hemophilia A.
试验速览
- 阶段
- 1 期
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- Pharmacokinetic parameters between test preparation and reference preparation, peak plasma concentration (Cmax)
研究概览
简要总结
This is a multi-center, open-label, randomized study. Participants will be assigned to A or B groups with a scale of 1:1 , i.e. infuse study drug followed by Xyntha (group A), or the alternate sequence (group B). All participants who completed the study will enter the Prophylactic Therapy Study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hemophilia A.
- •FVIII:C <1%. 3）12 and 65 years old.
- •4）Has received FVIII treatment and the treatment exposure days ≥
- •5）Has bleeding treatment records of at least 3 months before randomization. 6）FVIII inhibitor assay results is negative.
- •7） Subjects should agree to use an adequate method of contraception during the study.
- •8）Understood and Signed an informed consent form. 9）Has not received an treatment of any FVIII within 4 days before the first dose.
- •10）Non-bleeding state.
排除标准
- •Has a history or family history of blood coagulation factor VIII inhibitor.
- •Has other coagulation dysfunction diseases in addition to hemophilia A.
- •HIV positive.
- •Plan to receive surgery during the trial.
- •Has used immunomodulator within one weeks before the first dose，and less than 7 half-life periods.
- •Known to be allergic to experimental drugs or any excipients.
- •Severe anemia and need blood transfusion.
- •Serious liver or kidney damage.
- •Serious heart disease.
- •Uncontrollable hypertension.
- •Has participated in other clinical studies within one month before the first dose.
- •The researchers believe that it is not suitable for participants.
研究组 & 干预措施
group A
Participants will be assigned to group A or B with a scale of 1:1 , i.e. infuse reference drug Xyntha (group A), then experimental drug (group B). All participants who completed the study will enter the prophylaxis group study.
干预措施: Xyntha (Drug)
group A
Participants will be assigned to group A or B with a scale of 1:1 , i.e. infuse reference drug Xyntha (group A), then experimental drug (group B). All participants who completed the study will enter the prophylaxis group study.
干预措施: Recombinant Coagulation Factor VIII Injection (Drug)
group B
Participants will be assigned to group A or B with a scale of 1:1 , i.e. infuse experimental drug (group B), then reference drug Xyntha (group A). All participants who completed the study will enter the prophylaxis group study.
干预措施: Xyntha (Drug)
group B
Participants will be assigned to group A or B with a scale of 1:1 , i.e. infuse experimental drug (group B), then reference drug Xyntha (group A). All participants who completed the study will enter the prophylaxis group study.
干预措施: Recombinant Coagulation Factor VIII Injection (Drug)
结局指标
主要结局
Pharmacokinetic parameters between test preparation and reference preparation, peak plasma concentration (Cmax)
时间窗: Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.
Cmax is the maximum plasma concentration of Recombinant Coagulation Factor VIII or metabolite(s).
Pharmacokinetic parameters between Recombinant Coagulation Factor VIII, Area under the plasma concentration verus time curve(AUC)
时间窗: Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of area under the plasma concentration time curve from zero to infinity.
Incremental recovery between test preparation and reference preparation
时间窗: up to 24 weeks
Peak activity of FVIII (as Cmax) measured within 1 hour after the end of infusion.
次要结局
- tmax(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.)
- Peak plasma concentration (Cmax)(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on multiple dose in day 5 to day 8.)
- Mean time of residence (MRT)(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.)
- λz(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.)
- Vz(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.)
- Recombinant Coagulation Factor VIII multiple dose:tmax(On the 176th day after the prevention of medication)
- CL(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on single dose in day 1 to day 4.)
- Area under the plasma concentration verus time curve (AUC)(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on multiple dose in day 5 to day 8.)
- Recombinant Coagulation Factor VIII multiple dose:t1/2(On the 176th day after the prevention of medication)
- Recombinant Coagulation Factor VIII multiple dose:λz(On the 176th day after the prevention of medication)
- t1/2(Hour 30min (pre-dose), 5min, 20min, 35min, 60min, 1.5 h, 2h, 3 h, 6 h, 9 h, 24 h, 36 h, 48 h post-dose on multiple dose in day 5 to day 8.)
- Recombinant Coagulation Factor VIII multiple dose:CL(On the 176th day after the prevention of medication)
- Recombinant Coagulation Factor VIII multiple dose:Vz(On the 176th day after the prevention of medication)