Pharmacokinetics Evaluation of Recombinant Coagulation Factor VIII Injection in Subjects With Hemophilia A.

Overview

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.

Full Title of Study: “Randomized, Open-label, Double Cycle, Crossover, Pharmacokinetics Study of Recombinant Coagulation Factor VIII Injection Versus Xyntha® in Subjects With Hemophilia A.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2020

Interventions

  • Drug: Xyntha
    • Recombinant Coagulation Factor VIII Injection produced by Pfizer Inc.
  • Drug: Recombinant Coagulation Factor VIII Injection
    • A kind of Recombinant Coagulation Factor VIII Injection produced by sponsor.

Arms, Groups and Cohorts

  • Experimental: 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.
  • Experimental: 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.

Clinical Trial Outcome Measures

Primary Measures

  • Pharmacokinetic parameters between test preparation and reference preparation, peak plasma concentration (Cmax)
    • Time Frame: 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)
    • Time Frame: 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
    • Time Frame: up to 24 weeks
    • Peak activity of FVIII (as Cmax) measured within 1 hour after the end of infusion.

Secondary Measures

  • tmax
    • Time Frame: 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
  • t1/2
    • Time Frame: 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
  • Mean time of residence (MRT)
    • Time Frame: 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
    • Time Frame: 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.
  • CL
    • Time Frame: 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.
  • Vz
    • Time Frame: 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.
  • Area under the plasma concentration verus time curve (AUC)
    • Time Frame: 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.
  • Peak plasma concentration (Cmax)
    • Time Frame: 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.
  • Recombinant Coagulation Factor VIII multiple dose:tmax
    • Time Frame: 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.
  • Recombinant Coagulation Factor VIII multiple dose:t1/2
    • Time Frame: 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
    • Time Frame: On the 176th day after the prevention of medication
    • To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
  • Recombinant Coagulation Factor VIII multiple dose:CL
    • Time Frame: 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
    • Time Frame: 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.

Participating in This Clinical Trial

Inclusion Criteria

1. Hemophilia A. 2. 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. Exclusion Criteria:

1. Has a history or family history of blood coagulation factor VIII inhibitor. 2. Has other coagulation dysfunction diseases in addition to hemophilia A. 3. HIV positive. 4. Plan to receive surgery during the trial. 5. Has used immunomodulator within one weeks before the first dose,and less than 7 half-life periods. 6. Known to be allergic to experimental drugs or any excipients. 7. Severe anemia and need blood transfusion. 8. Serious liver or kidney damage. 9. Serious heart disease. 10. Uncontrollable hypertension. 11. Has participated in other clinical studies within one month before the first dose. 12. The researchers believe that it is not suitable for participants.

Gender Eligibility: All

Minimum Age: 12 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Lei Zhang, Doctor, 022-20909240, zhanglei1@ihcams.ac.cn

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