rFVIIa Prophylaxis in Children With Hemophilia A and Inhibitors

Study Overview
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Brief Summary
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The study evaluates the efficacy and safety of a prophylactic treatment with recombinant activated FVII in reducing the frequency of joint bleeds and the development of joint damage in children with hemophilia A who develop high-titer inhibitors.

Detailed Description
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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.

Official Title
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An Investigator-initiated Study on rFVIIa Prophylaxis in Children With Hemophilia A and Inhibitors - European Initiative to Prevent Joint Damage in Hemophilia A Children With Inhibitors

Conditions
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Hemophilia A With Inhibitors

Intervention / Treatment
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* Drug: recombinant activated factor VII
* Drug: recombinant activated factor VII


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 8 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prophylaxis<br>prophylaxis with recombinant activated FVII 90 µg/kg/day i.v. | Drug: recombinant activated factor VII<br>* 90 µg/kg/day i.v.<br>* Other names: NovoSeven;|
| Active Comparator: on demand treatment<br>treatment of bleeding episodes with 270 µg/kg (first/single dose) or 90 µg/kg i.v. every 2-3 hours until bleeding resolution | Drug: recombinant activated factor VII<br>* treatment of bleeding episodes with 270 µg/kg (first/single dose) or 90 µg/kg i.v. every 2-3 hours until bleeding resolution<br>* Other names: NovoSeven;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of joint bleeds. |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint status evaluated by the Hemophilia Joint Health Score |  | 18 months | 
| Number of adverse events and serious adverse events. |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemophilia A, inhibitors, prophylaxis, immune tolerance induction