Early Prophylaxis Immunologic Challenge (EPIC) Study

A Phase 3b Clinical Study to Assess Whether Regular Administration of ADVATE in the Absence of Immunological Danger Signals Reduces the Incidence Rate of Inhibitors in Previously Untreated Patients With Hemophilia A

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.

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