Survey of Inhibitors in Plasma-Product Exposed Toddlers

Patients meeting the enrollment criteria will be consecutively enrolled at each
participating centre, randomized to be treated exclusively with a single FVIII product
either plasma-derived or recombinant, and followed up until inhibitor development or until
50 exposure days (EDs) or 3 years from enrolment have elapsed, whichever comes first. Study
products, belonging to the class of rFVIII concentrates and to the class of plasma-derived
VWF/FVIII concentrates, will be provided for free to the patients for all the duration of
the study

Inclusion Criteria:

- Male subjects

- Any ethnicity

- Age <6 years

- Severe haemophilia A (FVIII:C <1%), as confirmed at enrolment by the central
laboratory.

o Those patients diagnosed locally as severe but subsequently found to have FVIII
levels >= 1% on testing at the central laboratory will be separately recorded in the
screening list.

- Previously untreated (0 EDs to any FVIII concentrates or blood products) or minimally
treated (<5 EDs) with blood components, namely whole blood, fresh frozen plasma,
packed red blood cells, platelets or cryoprecipitate.

o Patients not meeting these criteria will be separately recorded in the screening
list.

- Negative inhibitor measurement at both local and central laboratory at screening

- Ability to comply with study requirements

- Signed informed consent of legal tutors o Patients who will not accept to enter into
the study or to be randomized will be separately recorded.

Exclusion Criteria:

- Previous history of FVIII inhibitor

- Other congenital or acquired bleeding defects

- Plasma FVIII level >= 1%, as assayed at the central laboratory

o Those patients originally diagnosed locally as severe but subsequently found to
have FVIII levels ranging from 1% to 2% on testing at the central laboratory will be
separately recorded in the screening list.

- Concomitant congenital or acquired immunodeficiency

- Concomitant treatment with systemic immunosuppressive drugs

- Concomitant treatment with any investigational drug