Early Prophylaxis Immunologic Challenge (EPIC) Study

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