Early Prophylaxis Immunologic Challenge (EPIC) Study
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM)
Intervention description: Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose.
Intervention MeSH terms: Factor VIII
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: Male
Maximum age: 1 Year
Healthy volunteers: No

Summary:

      The purpose of the study was to assess if a once-weekly prophylactic regimen of 25 IU/kg
      ADVATE started at or before 1 year of age and before the onset of a severe bleeding phenotype
      (ie, joint bleeding), together with the minimization of immunological danger signals, can
      reduce the incidence rate of inhibitor formation in PUPs with severe and moderately severe
      hemophilia A.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with severe and moderately severe hemophilia A (FVIII ≤ 2%)

          -  Participants < 1 year of age

          -  Participants must have ≤ 3 exposure days (EDs) to any FVIII concentrate or
             FVIII-containing product used for treatment of minor bleeds (bleeds requiring no more
             than 2 infusions per event), or for preventative or precautionary infusions following
             possible injury

          -  Participants with prior circumcision are allowed to enroll only if bleeding issues
             related to circumcision were the cause for the original diagnosis of hemophilia A and
             no more than 2 EDs of FVIII treatment were required

          -  Adequate venous access (without need for central venous access device
             (CVAD)-placement) as determined by the physician

          -  Written informed consent from legally authorized representative(s)

        Exclusion Criteria:

          -  Life-threatening conditions (intracranial hemorrhage, severe trauma) or requirement
             for surgery at the time of enrollment

          -  Evidence of inhibitor ≥ 0.6 Bethesda Unit (BU) in Nijmegen-modified Bethesda Assay at
             study start (samples may be retested using lupus-insensitive inhibitor tests to reduce
             the number of false positive inhibitor test results)

          -  Inherited or acquired hemostatic defect other than hemophilia A

          -  Any clinically significant, chronic disease other than hemophilia A

          -  Known hypersensitivity to ADVATE or any of its constituents

          -  Any planned elective surgery that cannot be postponed until after the first 20 EDs

          -  Participation in the Hemophilia Inhibitor Previously Untreated Patient Study

          -  Application of red blood cell, platelet, or leukocyte concentrates, or plasma

          -  Administration of any medication affecting coagulation or platelet function

          -  Systemic administration of any immunomodulatory drug (eg, chemotherapy, intravenous
             glucocorticoids)

          -  Participation in another clinical study involving an investigational product (IP) or
             device within 30 days prior to study enrollment or during the course of this study