Pharmacokinetics Evaluation of Recombinant Coagulation Factor VIII Injection in Subjects With Hemophilia A.
- Conditions
- Hemophilia A
- Interventions
- Drug: Recombinant Coagulation Factor VIII Injection
- Registration Number
- NCT04060836
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 24
- Hemophilia A.
- FVIII:C <1%. 3）12 and 65 years old.
4）Has received FVIII treatment and the treatment exposure days ≥100. 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description group A Recombinant Coagulation Factor VIII Injection 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. group B Recombinant Coagulation Factor VIII Injection 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. group B Xyntha 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. group A Xyntha 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.
- Primary Outcome Measures
Name Time Method Pharmacokinetic parameters between test preparation and reference preparation, 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 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) 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 up to 24 weeks Peak activity of FVIII (as Cmax) measured within 1 hour after the end of infusion.
- Secondary Outcome Measures
Name Time Method 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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of time to reach maximum plasma concentration
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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of maximum plasma concentration.
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. MRT is the average time that drug molecules stay in the body after a quick intravenous injection.
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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent volume of distribution.
Recombinant Coagulation Factor VIII multiple dose:tmax On the 176th day after the prevention of medication To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of time to reach maximum plasma concentration.
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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent plasma clearance following intravenous injection.
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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of area under the plasma concentration time curve from zero to infinity.
Recombinant Coagulation Factor VIII multiple dose:t1/2 On the 176th day after the prevention of medication To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of half-life.
Recombinant Coagulation Factor VIII multiple dose:λz On the 176th day after the prevention of medication To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
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. To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of half-life
Recombinant Coagulation Factor VIII multiple dose:CL On the 176th day after the prevention of medication To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent plasma clearance following intravenous injection.
Recombinant Coagulation Factor VIII multiple dose:Vz On the 176th day after the prevention of medication To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent volume of distribution.
Trial Locations
- Locations (5)
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
HeNan Cancer Provincial Hospital
🇨🇳Zhengzhou, Henan, China
AnHui Provincial Hospital
🇨🇳Hefei, Anhui, China
The First Hospital of LanZhou University
🇨🇳Lanzhou, Gansu, China
Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
🇨🇳Tianjin, Tianjin, China