rFVIIa Prophylaxis in Children With Hemophilia A and Inhibitors

This is a multicentre, randomised, controlled study designed to gain evidence of the
advantage of the prophylactic, daily treatment with recombinant activated FVII as compared
to the conventional on demand therapy in reducing the bleeding frequency and preserving the
orthopaedic status in hemophilic children with inhibitors.

Inclusion Criteria:

- Patients with hemophilia A who have been treated with factor VIII on demand or on
prophylaxis and who have developed inhibitors to factor VIII

- ≤ 2 years from the time of first inhibitor detection.

- High-responding inhibitors (historical peak > 5 BU/mL)and known anamnestic response
in case of negative inhibitor titre.

- Candidates to start daily ITI with FVIII doses ranging from 50 IU/Kg/day to 200
IU/Kg/day

- Maximal two bleedings in the same joint within the last 6 months before entering
the study or maximal six joint bleeds in the same joint within 2 years

- Adequate venous access for daily infusion and capable (caregiver) of reconstituting
and injecting the study drug

- Informed consent by parents or legal guardians.

Exclusion Criteria:

- ITI already started

- Known or suspected hypersensitivity to the active substance or to any of the
excipients of the study drug

- Administration of any investigational product within 30 days prior to randomisation

- Other coagulation disorders than congenital hemophilia A.

- Family history of thrombosis at an early age (< 40 years), known thrombophilia, any
previous thrombosis including catheter-related deep vein thrombosis, previous
neonatal thrombosis.

- Known pseudo tumours

- Known severe liver disease

- Platelet count < 50,000 platelets/µL at screening

- Surgery within one month or planned major and/or orthopaedic surgery.