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

Primary Purpose

Hemophilia A

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Xyntha
Recombinant Coagulation Factor VIII Injection
Sponsored by
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hemophilia A

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • AnHui Provincial HospitalRecruiting
  • The First Hospital of LanZhou UniversityRecruiting
  • HeNan Cancer Provincial HospitalRecruiting
  • Xiangya Hospital Central South UniversityRecruiting
  • Hematology and Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

group A

group B

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Pharmacokinetic parameters between test preparation and reference preparation, peak plasma concentration (Cmax)
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)
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
Peak activity of FVIII (as Cmax) measured within 1 hour after the end of infusion.

Secondary Outcome Measures

tmax
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of time to reach maximum plasma concentration
t1/2
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of half-life
Mean time of residence (MRT)
MRT is the average time that drug molecules stay in the body after a quick intravenous injection.
λz
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
CL
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent plasma clearance following intravenous injection.
Vz
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)
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)
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of maximum plasma concentration.
Recombinant Coagulation Factor VIII multiple dose:tmax
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
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of half-life.
Recombinant Coagulation Factor VIII multiple dose:λz
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
Recombinant Coagulation Factor VIII multiple dose:CL
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
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent volume of distribution.

Full Information

First Posted
July 16, 2019
Last Updated
August 16, 2019
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04060836
Brief Title
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

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 8, 2019 (Actual)
Primary Completion Date
March 2020 (Anticipated)
Study Completion Date
March 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
group A
Arm Type
Experimental
Arm Description
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.
Arm Title
group B
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Xyntha
Intervention Description
Recombinant Coagulation Factor VIII Injection produced by Pfizer Inc.
Intervention Type
Drug
Intervention Name(s)
Recombinant Coagulation Factor VIII Injection
Intervention Description
A kind of Recombinant Coagulation Factor VIII Injection produced by sponsor.
Primary Outcome Measure Information:
Title
Pharmacokinetic parameters between test preparation and reference preparation, peak plasma concentration (Cmax)
Description
Cmax is the maximum plasma concentration of Recombinant Coagulation Factor VIII or metabolite(s).
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.
Title
Pharmacokinetic parameters between Recombinant Coagulation Factor VIII, Area under the plasma concentration verus time curve(AUC)
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of area under the plasma concentration time curve from zero to infinity.
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.
Title
Incremental recovery between test preparation and reference preparation
Description
Peak activity of FVIII (as Cmax) measured within 1 hour after the end of infusion.
Time Frame
up to 24 weeks
Secondary Outcome Measure Information:
Title
tmax
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of time to reach maximum plasma concentration
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.
Title
t1/2
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of half-life
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.
Title
Mean time of residence (MRT)
Description
MRT is the average time that drug molecules stay in the body after a quick intravenous injection.
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.
Title
λz
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
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.
Title
CL
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent plasma clearance following intravenous injection.
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.
Title
Vz
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent volume of distribution.
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.
Title
Area under the plasma concentration verus time curve (AUC)
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of area under the plasma concentration time curve from zero to infinity.
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.
Title
Peak plasma concentration (Cmax)
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of maximum plasma concentration.
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.
Title
Recombinant Coagulation Factor VIII multiple dose:tmax
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of time to reach maximum plasma concentration.
Time Frame
On the 176th day after the prevention of medication
Title
Recombinant Coagulation Factor VIII multiple dose:t1/2
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of half-life.
Time Frame
On the 176th day after the prevention of medication
Title
Recombinant Coagulation Factor VIII multiple dose:λz
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of terminal rate constant.
Time Frame
On the 176th day after the prevention of medication
Title
Recombinant Coagulation Factor VIII multiple dose:CL
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent plasma clearance following intravenous injection.
Time Frame
On the 176th day after the prevention of medication
Title
Recombinant Coagulation Factor VIII multiple dose:Vz
Description
To characterize the pharmacokinetics of Recombinant Coagulation Factor VIII by assessment of apparent volume of distribution.
Time Frame
On the 176th day after the prevention of medication

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Zhang, Doctor
Phone
022-20909240
Email
zhanglei1@ihcams.ac.cn
Facility Information:
Facility Name
AnHui Provincial Hospital
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zimin Sun, Doctor
Phone
0551 -62283191
Email
zmsun_vip@163.com
First Name & Middle Initial & Last Name & Degree
Zimin Sun
Facility Name
The First Hospital of LanZhou University
City
Lanzhou
State/Province
Gansu
ZIP/Postal Code
730000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yaming Xi, Doctor
Phone
0931-8356266
Email
xiyaming@163.com
First Name & Middle Initial & Last Name & Degree
Yaming Xi
Facility Name
HeNan Cancer Provincial Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hu Zhou, Doctor
Phone
0371-65587278
Email
"papertigerhu@163.com
First Name & Middle Initial & Last Name & Degree
Hu Zhou
Facility Name
Xiangya Hospital Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xielan Zhao, Doctor
Phone
0731-84327564
Email
zhaoxl9198@163.com
First Name & Middle Initial & Last Name & Degree
Xielan Zhao
Facility Name
Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, Doctor
Phone
022-20909240
Email
zhanglei1@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Lei Zhang

12. IPD Sharing Statement

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

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