Dose-Response 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; Antihemophilic factor, recombinant, manufactured protein-free
Intervention description: 15 IU/kg rAHF-PFM; 30 IU/kg rAHF-PFM; 50 IU/kg rAHF-PFM
Intervention MeSH terms: Factor VIII
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the effect of 3 doses of ADVATE rAHF-PFM on initial
      recovery (% increase [IU/dL] per IU/kg infused) and major single-infusion pharmacokinetic
      parameters. The 3 doses are 15, 30, and 50 IU/kg. Prior to each infusion, subjects will not
      have received treatment with a factor VIII concentrate for at least 3 days. Blood samples
      will be drawn within 30 minutes pre-infusion and at 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32 and 48
      hours post-infusion. A washout period of at least 3 days, but no more than 30 days between
      the last blood draw and the next infusion will be observed. During participation, subjects
      will maintain their preexisting treatment regimens with ADVATE rAHF-PFM or other factor VIII
      concentrate.

      A secondary objective is to investigate the relationship between pharmacokinetic parameters
      at each dose level and the levels of von Willebrand factor ristocetin cofactor activity and
      von Willebrand factor antigen at baseline.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has severe hemophilia A as defined by a baseline factor VIII activity <1%
             of normal; tested at screening. (A minimum washout period of 3 days is required before
             the blood sample can be drawn to determine baseline factor VIII levels.)

          -  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 12 to 65 years of age.

          -  The subject has a Karnofsky performance score >60.

          -  The subject is human immunodeficiency virus negative (HIV-) or HIV+ with CD4 count
             >=400 cells/mm3 (CD4 count determined at screening, if necessary).

          -  The subject or subject´s legally authorized representative has provided written
             informed consent.

        Exclusion Criteria:

          -  The subject has a known hypersensitivity to mouse or hamster proteins or to factor
             VIII concentrates.

          -  The subject has a history of factor VIII inhibitors with titer >=0.8 BU (Bethesda
             Assay) or >=0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to
             screening.

          -  The subject has a detectable factor VIII inhibitor at screening, >=0.4 BU (Nijmegen
             modification of the Bethesda Assay), in the Baxter 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 participated in another investigational study within 30 days of
             enrollment.

          -  The subject´s clinical condition may require a major or moderate surgery (estimated
             blood loss >500 mL) during the period of participation in the study.