Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Antihemophilic factor, recombinant, manufactured protein-free; Antihemophilic factor, recombinant, manufactured protein-free
Intervention description: Standard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator; PK-driven prophylaxis: 20-80 IU/kg every 72+/-6 hours, actual dose determined by Baxter using an algorithm and the patient´s pharmacokinetic data
Intervention MeSH terms: Factor VIII
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Minimum age: 7 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary purpose of this randomized, two-arm parallel clinical study in 66 previously
      treated patients with severe or moderately severe hemophilia A is to compare the rate of
      bleeding episodes for standard prophylaxis (20-40 IU/kg every 48 ± 6 hours; actual dose
      determined by the investigator) with that of alternate prophylaxis (20-80 IU/kg every 72 + 6
      hours; actual dose determined by Baxter utilizing an algorithm and the patient's
      pharmacokinetic data). The rates of bleeding episodes for the on-demand regimen and the
      prophylaxis regimens will also be compared for the cross-over portion of the study. Enrolled
      patients will be treated originally on demand for a period of 6 months and then they will be
      randomized into one of the prophylaxis arms. Prophylactic treatment will last for a period of
      12 months +/- 2 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has severe or moderately severe hemophilia A as defined by a baseline
             factor VIII level <= 2% of normal, as tested at screening

          -  The subject has a documented history of at least 150 exposure days to factor VIII
             concentrates (either plasma-derived or recombinant)

          -  The subject is within 7 to 65 years of age

          -  The subject has a Karnofsky performance score > (greater than) 60

          -  The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4
             count >= 400 cells/mm³ (CD4 count determined at screening, if necessary)

          -  The subject has been on a documented on-demand treatment regimen for at least 12
             months immediately prior to enrollment

          -  The subject has a documented history (e.g. in medical charts or dispensing
             information, or signed investigator statement) of at least 8 joint hemorrhages in the
             12 months immediately prior to enrollment

          -  The subject resides within the coverage area of the mobile compliance device; coverage
             area will be determined at screening

          -  The subject or the subject's legally authorized representative has provided written
             informed consent

        Exclusion Criteria:

          -  The subject has a known hypersensitivity to factor VIII concentrates or mouse or
             hamster proteins

          -  The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by
             Bethesda or Nijmegen assay) at any time prior to screening

          -  The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4
             BU (by Nijmegen Assay) in the central laboratory

          -  The subject has severe chronic liver disease as evidenced by, but not limited to, any
             of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal
             vein hypertension including presence of otherwise unexplained splenomegaly and history
             of esophageal varices.

          -  The subject has been diagnosed with an inherited or acquired hemostatic defect other
             than hemophilia A (e.g., qualitative platelet defect or von Willebrand's Disease)

          -  The subject has been treated during the last sixty (60) days prior to or is being
             treated at screening/enrollment with an immunomodulating drug.

          -  The subject has participated in another investigational study within thirty (30) days
             of enrollment

          -  The subject has previously participated in a clinical study with rAHF-PFM

          -  The subject's clinical condition may require a major surgery (defined as moderate to
             critical risk and perioperative blood loss ≥ 500 mL) during the period of the
             subject's participation in the study

          -  The subject is female of childbearing potential with a positive pregnancy test