Clinical trial NCT05487976: Clinical Study of Recombinant Human Activated Coagulation Factor VII for Injection in Patients With Hemophilia With Inhibitor
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hemophilia A
Hemophilia B
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

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

  1. FⅧ\<1% or FIX activity\<2%;
  2. FⅧ inhibitor or FⅨ 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 FⅦ 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.

Primary outcomes:
measure: Number of bleeding Effective rate of hemostasis
timeFrame: Each new blood event was assessed within 12 hours of initial treatment
measure: Activity recovery of first dose
timeFrame: Within 1 hour of completion of infusion
Secondary outcomes:
measure: Number of bleeding effective rate of hemostasis within 8 hours
timeFrame: Each new blood event was assessed within 8 hours of initial treatment
measure: Number of bleeding effective rate continuous hemostatic
timeFrame: Each new blood event was assessed within 24 hours of initial treatment
measure: Activity recovery after repeated administration
timeFrame: Within 1 hour of completion of infusion
measure: Dose of injections for each new blood transfusion
timeFrame: Up to 24 weeks.
measure: Number of injections for each new blood transfusion
timeFrame: Up to 24 weeks.
measure: Coagulation tests
timeFrame: First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
measure: Coagulation tests
timeFrame: First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
measure: Coagulation tests
timeFrame: First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
measure: Coagulation tests
timeFrame: First and week 24, within 30 minutes before the administration and 5 minutes after the completion of drug injection.
measure: Coagulation tests
timeFrame: First and week 24，within 30 minutes before the administration and 5 minutes after the completion of drug injection.
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Tangshan
country: China
facility: Affiliated Hospital of North China University of Science and Technology
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Tianjin
country: China
facility: Hematology Hospital of Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
References: