Efficacy and Safety Study of Prophylactic Versus On-Demand Treatment With Feiba NF in Subjects With Hemophilia A or B and a High Titer Inhibitor
Condition: Hemophilia A or B With Inhibitors; Hemophilia A; Hemophilia B
MeSH terms: Hemophilia A; Hemophilia B
Intervention: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated); Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
Intervention description: 85 ± 15 U/kg of FEIBA NF every other day during the 12-month prophylactic period; FEIBA NF dose and dosing interval as prescribed by the treating physician
Intervention MeSH terms: Factor VIII; Anti-inhibitor coagulant complex
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 4 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hemophilia A; Factor VIII Inhibitor; Factor IX Inhibitor; Hemophilia B

Summary:

      The purpose of the study was to determine the efficacy, safety, and health-related quality of
      life benefits with FEIBA NF prophylactic treatment as compared with on-demand treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated informed consent form by the participant or the participant's legally
             authorized representative

          -  The participant is ≥ 4 to ≤ 65 years of age

          -  The participant has a Karnofsky performance score of ≥ 60

          -  Hemophilia A and B of any severity, with documented history of high-titer inhibitor (>
             5 Bethesda unit (BU)) for at least 12 months; or, if inhibitor titer is ≤ 5 BU, and
             the participant is refractory with increased dosing of either factor VIII (FVIII) or
             factor IX (FIX), as demonstrated from the participant's medical history

          -  Currently being treated on an on-demand basis for treatment of bleeding episodes

          -  Adequate venous access, with or without central venous device

          -  ≥ 12 bleeding episodes requiring treatment with by-passing agents in the past 12
             months, based on medical history

          -  Competent in-home treatment and infusion therapy

          -  Currently using bypassing agents (activated prothrombin complex concentrate (APCC) or
             recombinant activated factor VII (rFVIIa)) for treatment of bleeding episodes

          -  HCV-, either by antibody testing or polymerase chain reaction (PCR); or HCV+ with
             stable hepatic disease

          -  HIV-, or HIV+ with stable disease and CD4 count > 200 cells/mm3 at screening

          -  Female participant of childbearing potential, presents with a negative serum pregnancy
             test, and agrees to employ adequate birth control measures for the duration of the
             study

        Exclusion Criteria:

          -  Currently receiving immune tolerance induction (ITI)

          -  Currently on regular prophylactic therapy to prevent bleeding episodes

          -  Clinically symptomatic liver disease (e.g. diagnosis of cirrhosis [confirmed by liver
             biopsy], portal vein hypertension, ascites, prothrombin time (PT) 5 seconds above
             upper limit of normal)

          -  Platelet count < 100,000/ml

          -  Planned elective surgery during participation in this study

          -  Participant is currently participating in another clinical study and has received an
             investigational product or device within 30 days prior to study entry

          -  Planned use of pegylated or non-pegylated alpha-interferon with or without ribavirin
             for HCV infected participants or planned use of a protease inhibitor for HIV infected
             participants. Participants currently taking any of these medications for a 30-day
             course are eligible.

          -  Clinically significant increase in D-dimer levels from historical baseline and/or
             associated with chronic liver disease or clinically evident thromboembolic event

          -  Known hypersensitivity to anti-inhibitor coagulant complexes (AICCs)

          -  Currently treated with a systemic immunomodulating drug

          -  Prior history of thromboembolic event: acute myocardial infarction, deep vein
             thrombosis, or pulmonary embolism

          -  Diagnosis of advanced atherosclerosis, malignancy and/or other diseases that may
             increase the participant's risk of thromboembolic complications

          -  Clinically significant medical, psychiatric, or cognitive illness, or recreational
             drug/alcohol use that, in the opinion of the investigator, would affect participant
             safety or compliance