Survey of Inhibitors in Plasma-Product Exposed Toddlers

Inhibitor Development in Previously Untreated Patients (PUPs) or Minimally Blood Component-Treated Patients (MBCTPs) When Exposed to Plasma-derived Von Willebrand Factor-Containing Factor VIII (VWF/FVIII) Concentrates and to Recombinant Factor VIII (rFVIII) Concentrates: An Independent, International, Multicentre, Prospective, Controlled, Randomised, Open Label, Clinical Trial

The primary objective of the study is to assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in previously untreated patients (PUPs) or minimally blood component-treated (MBCTPs) in the first 50 EDs or in the first 3 years from enrollment, whichever occurs first.

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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