Clinical trial NCT04060836: Pharmacokinetics Evaluation of Recombinant Coagulation Factor VIII Injection in Subjects With Hemophilia A.
Official title: Randomized, Open-label, Double Cycle, Crossover, Pharmacokinetics Study of Recombinant Coagulation Factor VIII Injection Versus Xyntha® in Subjects With Hemophilia A.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hemophilia A
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-08-19
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameters between test preparation and reference preparation, peak plasma concentration (Cmax)
timeFrame: 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.
measure: Pharmacokinetic parameters between Recombinant Coagulation Factor VIII, Area under the plasma concentration verus time curve(AUC)
timeFrame: 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.
measure: Incremental recovery between test preparation and reference preparation
timeFrame: up to 24 weeks
Secondary outcomes:
measure: tmax
timeFrame: 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.
measure: t1/2
timeFrame: 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.
measure: Mean time of residence (MRT)
timeFrame: 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.
measure: λz
timeFrame: 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.
measure: CL
timeFrame: 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.
measure: Vz
timeFrame: 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.
measure: Area under the plasma concentration verus time curve (AUC)
timeFrame: 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.
measure: Peak plasma concentration (Cmax)
timeFrame: 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.
measure: Recombinant Coagulation Factor VIII multiple dose:tmax
timeFrame: On the 176th day after the prevention of medication
measure: Recombinant Coagulation Factor VIII multiple dose:t1/2
timeFrame: On the 176th day after the prevention of medication
measure: Recombinant Coagulation Factor VIII multiple dose:λz
timeFrame: On the 176th day after the prevention of medication
measure: Recombinant Coagulation Factor VIII multiple dose:CL
timeFrame: On the 176th day after the prevention of medication
measure: Recombinant Coagulation Factor VIII multiple dose:Vz
timeFrame: On the 176th day after the prevention of medication
Other outcomes:
Locations:
city: Hefei
country: China
facility: AnHui Provincial Hospital
state: Anhui
city: Lanzhou
country: China
facility: The First Hospital of LanZhou University
state: Gansu
city: Zhengzhou
country: China
facility: HeNan Cancer Provincial Hospital
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Tianjin
country: China
facility: Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
References: