Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors
Condition: Hemophilia A With Inhibitors; Hemophilia B With Inhibitors
MeSH terms: Hemophilia A; Hemophilia B
Intervention: Coagulation Factor VIIa (Recombinant)
Intervention description: A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Male
Minimum age: 12 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate
      dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the
      treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor
      VIII/IX
    

Eligibility criteria:

        Inclusion Criteria:

          -  be male with a diagnosis of congenital hemophilia A and/or B of any severity

          -  have one of the following:

          -  a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the
             institutional lab), OR

          -  a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as
             demonstrated from the subject's medical history, precluding the use of Factor VIII or
             IX products to treat bleedings, OR

          -  a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as
             demonstrated from the subject's medical history, precluding the use of Factor VIII or
             IX products to treat bleedings

          -  be 12 years or older, up to and including 75 years of age (NOTE: different age
             restrictions may apply per local regulation and/or ethical considerations)

          -  have at least 3 bleeding episodes of any severity in the past 6 months be capable of
             understanding and willing to comply with the conditions of the protocol

          -  have read, understood and provided written informed consent (patient and/or
             parent(s)/legal guardian(s) if <18 years of age)

        Exclusion Criteria:

          -  have any coagulation disorder other than hemophilia A or B

          -  be immuno-suppressed (i.e., the patient should not be receiving systemic
             immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening
             should be >200/µl)

          -  have a known allergy or hypersensitivity to rabbits

          -  have platelet count <100,000/mL

          -  have had within one month prior to first administration of the study drug in this
             study a major surgical procedure (e.g. orthopedic, abdominal)

          -  have received an investigational drug within 30 days of the first study drug
             administration, or is expected to receive such drug during participation in this study

          -  have a clinically relevant hepatic (AST and/or alanine aminotransferase (ALT) >3 times
             the upper limit of normal) and/or renal impairment (creatinine >2 times the upper
             limit of normal)

          -  have a history of arterial and/or venous thromboembolic events (such as myocardial
             infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or
             pulmonary embolism) within 2 years prior to first dose of study drug, or current New
             York Heart Association (NYHA) functional classification score of stage II -IV

          -  have an active malignancy (those with non-melanoma skin cancer are allowed)

          -  have any life-threatening disease or other disease or condition which, according to
             the investigator's judgment, could imply a potential hazard to the patient, interfere
             with the trial participation or trial outcome (e.g., a history of non-responsiveness
             to bypassing products).