Clinical Study of Recombinant Human Activated Coagulation Factor VII for Injection in Patients With Hemophilia With Inhibitor

Hemophilia A Clinical Trial

Official title:

A Phase III Clinical Study of the Efficacy and Safety of Recombinant Human Activated Coagulation Factor VII for Injection in Patients With Hemophilia With Inhibitors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05487976
• Other study ID #: TQG203-III-01
• Status: Recruiting
• Phase: Phase 3
• Start date: April 28, 2022
• Est. completion date: April 2023

Study information

• Verified date: August 2022
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Lei Zhang, Doctor
• Phone: 13502118379
• Email: zhanglei1[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Human coagulation factor VII is a vitamin K-dependent serine endogenous protease, and its activated form plays an important role in the coagulation process. Recombinant human activated coagulation factor VII is an activated state coagulation factor VII obtained by recombinant means.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 1 Diagnosed as congenital hemophilia A or B, and meet the following conditions:

1. F?<1% or FIX activity<2%;

2. F? inhibitor or F? inhibitor titer in the screening period>5 BU (Nijmegen modified Bethesda method of detection)."

• 2 Age =18 and =65 years, male or female.
• 3 There have been at least two incidents of bleeding of any kind in the last six months.
• 4 No other drugs for the treatment of hemophilia have been used within 72hours (3 days) before administration, including prothrombin complex and any coagulation factor VII or activated coagulation factor VII?coagulation factor VIII?coagulation factor IX products, cryoprecipitate, fresh plasma and whole blood, etc.
• 5 Subjects of childbearing age agree to take effective contraceptive measures throughout the trial period, and continue to 28 days after the last medication.
• 6 Volunteer to participate in this study, sign an informed consent form, have good compliance, and be able to cooperate with the experimental observation.

Exclusion Criteria:

• 1 Any other bleeding disease except Congenital hemophilia A or B.
• 2 Patients with any previous medical history or symptoms of arterial or venous thromboembolic events (such as atherosclerosis, myocardial infarction, ischemic stroke, transient ischemic attack, deep vein thrombosis or pulmonary hypertension embolism) or disseminated intravascular coagulation (DIC) within the past 1 year.
• 3 Baseline and previous values of F? inhibitor or activated recombinant human coagulation factor VII inhibitor is positive.
• 4 Vitamin K deficiency.
• 5 Human immunodeficiency virus (HIV) positive and cluster of differentiation 4 (CD4) count =200/µl, the number of virus carriers =200 particles/µl or =400000 copies/ml.
• 6 Subjects plan to perform elective surgery during the trial period.
• 7 Those who are allergic to test drugs or any excipients.
• 8 Severe anemia and need blood transfusion.
• 9 Platelet count <80×10^9/L.
• 10 Obvious liver or kidney damage: glutamic-pyruvic transaminase (ALT) or aspartic transaminase (AST)>2.5×ULN, or total bilirubin>1.5×ULN or serum creatinine>1.5×ULN.
• 11 Severe heart disease, including myocardial infarction, cardiac insufficiency grade 3 or above, the current New York Heart Association cardiac function grade II-IV.
• 12 There was a prior intracranial hemorrhage
• 13 Those who had used or planned to use any anticoagulants, antifibrinants and drugs affecting platelet function during the first week of medication included non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin
• 14 Hypertension that cannot be controlled with drug treatment: systolic blood pressure> 150 mmHg or diastolic blood pressure> 90 mmHg.
• 15 Participated in other clinical studies (except Activated coagulation factor VII, coagulation factor VIII and coagulation factor IX trials) within one month before the first medication.
• 16 Alcoholism, drug abuse, mental disorders, other severe acute or chronic diseases, greater abnormal laboratory values, and those who are considered unsuitable by the researcher.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Drug:
• Recombinant human activated coagulation factor VII for injection
Human coagulation factor VII is a vitamin K-dependent serine endogenous protease, and its activated form plays an important role in the coagulation process. Recombinant human activated coagulation factor VII is an activated state coagulation factor VII obtained by recombinant means.

Locations

Country	Name	City	State
China	Xiangya Hospital Central South University	Changsha	Hunan
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Affiliated Hospital of North China University of Science and Technology	Tangshan	Hebei
China	Hematology Hospital of Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of bleeding Effective rate of hemostasis	Hemostasis is effective after the bleeding event if the bleeding event has not received other treatment within 12 hours since the first treatment and achieved moderate or above remission (based on the four-point scoring standard)	Each new blood event was assessed within 12 hours of initial treatment
Primary	Activity recovery of first dose	The peak coagulation factor VII activity measured within 1 hour after the end of the infusion was subtracted from the baseline coagulation factor VII activity and expressed as [IU/ml]/[IU/kg].	Within 1 hour of completion of infusion
Secondary	Number of bleeding effective rate of hemostasis within 8 hours	Excellent remission (based on the four-point scoring standard)	Each new blood event was assessed within 8 hours of initial treatment
Secondary	Number of bleeding effective rate continuous hemostatic	Moderate or above remission (based on grade 4 scoring criteria) without receiving other treatment within 24 hours after the occurrence of bleeding event is considered as effective hemostasis after the occurrence of bleeding event.	Each new blood event was assessed within 24 hours of initial treatment
Secondary	Activity recovery after repeated administration	The peak coagulation factor VII activity measured within 1 hour after the end of the infusion was subtracted from the baseline coagulation factor VII activity and expressed as [IU/ml]/[IU/kg].	Within 1 hour of completion of infusion
Secondary	Dose of injections for each new blood transfusion	Dose of injections for each new blood transfusion.The dose of injections (including average injection dose and total dose) of each new blood transfusion were recorded.	Up to 24 weeks.
Secondary	Number of injections for each new blood transfusion	Number of injections for each new blood transfusion.The number of injections of each new blood transfusion were recorded.	Up to 24 weeks.
Secondary	Coagulation tests	Coagulation tests: Changes of activated partial thromboplastin time (APTT).	First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
Secondary	Coagulation tests	Coagulation indicators: Changes of prothrombin time (PT).	First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
Secondary	Coagulation tests	Coagulation indicators: Changes of thrombin time(TT).	First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
Secondary	Coagulation tests	Coagulation indicators: Changes of fibrinogen (Fbg).	First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
Secondary	Coagulation tests	Coagulation indicators: thrombin production test (TGA):Changes of thrombin production potential (ETP) in TGA at each test time.	First and week 24,within 30 minutes before the administration and 5 minutes after the completion of drug injection.