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

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

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.

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.