Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Recombinant Factor VIII (Kogenate FS, BAY14-2222); Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Intervention description: Prophylaxis treatment includes three times per week administration of 25 IU/kg of Kogenate FS. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.; Treated according to the Kogenate FS package insert indications and study physician recommendations
Intervention MeSH terms: Factor VIII
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: Male
Minimum age: 12 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Hemophilia A

Summary:

      To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding
      frequency (number of bleeds per year) and on joint damage.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males aged 12 to 50 years (US and Argentina)

          -  Males aged 18 to 50 years (other countries)

          -  Subjects with severe hemophilia A (<1% FVIII:C) as confirmed by the central lab from a
             sample obtained at least 96 hours after FVIII administration wash-out. Allow for the
             inclusion of a maximum of 10% (n=8) of patients with 1-2% FVIII:C baseline levels as
             long as they exhibit clinical severity and comply with all other inclusion criteria.

          -  Subjects with at least 150 prior exposure days with any FVIII

          -  Subjects who have been on episodic treatment and no known regular prophylaxis
             treatment for more than 12 consecutive months in the previous 5 years

          -  Subjects with 6 to 24 bleeding events and/or treatments in the previous 6 months prior
             to study entry which are documented and available in the subjects medical records.
             Documentation can include records from previous physicians, specific home treatment
             records, emergency room or hospital records, x-ray reports, etc. The investigator can
             also document with a detailed note the number of bleeds reported by the subject in the
             last 6 months.

          -  Subjects with inhibitor formation surveillance (inhibitor or recovery testing) over
             the ten years prior to enrollment documented by the investigator and who do not have a
             history of any of the following:

               -  A positive inhibitor titer of 5.0 Bethesda Unit (BU) or greater by either BU
                  assay system at any time since first exposure to exogenous factor VIII

               -  A positive inhibitor test result of 1.0 or greater performed by the original BU
                  assay at any time in the past 10 years (A subject can have more than one positive
                  inhibitor test of 0.6 or greater by the original BU assay test but all must be
                  less than 1.0 BU using the original BU assay.)

               -  A positive inhibitor test result of 0.6 or greater performed by the Nijmegen
                  method at any time in the past 10 years

          -  Subjects with no inhibitor activity by Nijmegen-modified Bethesda assay, either
             positive (> 0.6 BU is considered positive) or borderline (> 0.3 and < 0.6 BU is
             considered borderline) as measured in the current study reference laboratory

        Exclusion Criteria:

          -  Subjects with any other bleeding disease besides hemophilia A (i.e. von Willebrand
             disease)

          -  Subjects with thrombocytopenia (platelets < 100,000/mm3)

          -  Subjects with abnormal renal function (Cockcroft-Gault Creatinine Clearance value of
             60 mL/min or lower)

          -  Subjects with active hepatic disease (Aspartate aminotransferase [AST] or Alanine
             aminotransferase [ALT] > 5xUpper Limit of Normal (ULN))

          -  Subjects on treatment with immunomodulatory agents within the last 3 months prior to
             study entry or during the study (the following drugs are however allowed: interferon-a
             treatment for Hepatitis C virus (HCV), Highly active anti-retroviral therapy (HAART)
             therapy for human immunodeficiency virus (HIV) and/or a total of two courses of pulse
             treatment with steroids for a maximum of 7 days at 1mg/kg or less)

          -  Subjects with an absolute CD4 lymphocyte cell count < 200 cells/mm3 (due to HIV, HCV
             or another suspected medical condition)

          -  Subjects with known hypersensitivity to rFVIII, mouse or hamster proteins

          -  Subjects who are receiving or had received other experimental drugs within 1 month
             prior to study entry

          -  Subjects who require any pre-medication to tolerate FVIII injections (e.g.
             anti-histamines)

          -  Subjects who are unwilling to comply with study visits or either of the possible
             treatment regimens

          -  Subjects who have a planned orthopedic intervention to be performed during the study
             that may substantially affect bleeding (e.g. surgical or chemical or radiological
             synovectomy)

          -  Subjects who are not suitable for participation in this study for any reason,
             according to the Investigator

          -  Subjects who have poor joint status as defined by routine need for a wheelchair or
             unable to ambulate without the assistance of a brace, cane or crutches

          -  Three or more joints that are already fused or "frozen" also called ankylosis