rFVIIa Prophylaxis in Children With Hemophilia A and Inhibitors

Phase 2

• Conditions: Hemophilia A With Inhibitors
• Interventions: Drug: recombinant activated factor VII

• Registration Number: NCT01105546
• Lead Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2010-04-15
• Study First Submitted QC: 2010-04-15
• Study First Posted: 2010-04-16
• Study Start: 2010-12
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-05
• Last Update Posted: 2013-04-08
• Primary Completion: 2014-02
• Study Completion: 2014-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
prophylaxis	recombinant activated factor VII	prophylaxis with recombinant activated FVII 90 µg/kg/day i.v.
on demand treatment	recombinant activated factor VII	treatment of bleeding episodes with 270 µg/kg (first/single dose) or 90 µg/kg i.v. every 2-3 hours until bleeding resolution

Primary Outcome Measures

Name	Time	Method
Total number of joint bleeds.	18 months

Secondary Outcome Measures

Name	Time	Method
Number of adverse events and serious adverse events.	18 months
Joint status evaluated by the Hemophilia Joint Health Score	18 months

Trial Locations

Locations (15)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Haemophilia Comprehensive Care Centre, Edouard Herriot University Hospital; 🇫🇷 Lyon, France

Klinikum der Johann Wolfgang Goethe-Universitat; 🇩🇪 Frankfurt/M, Germany

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

Unidad de Coagulopatias Congenitas, Hospital Universitario la Fe; 🇪🇸 Valencia, Spain

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

National Institute for Transfusional Hematology; 🇷🇴 Bucarest, Romania

Spitaluc Clinic de Urgenta pentru Copii Louis Turcanu, University of Medicine and Pharmacy; 🇷🇴 Timisoara, Romania

Vivantes Klinikum im Friedrichshain Haemophilia Care Center, Medical Center; 🇩🇪 Berlin, Germany

Klinikum Bremen-Mitte, Prof.-Hess-Kinderklinik; 🇩🇪 Bremen, Germany

Azienda Ospedaliero-Universitaria Careggi Agenzia per l'emofilia e Centro di riferimento regionale per i disordini congeniti del sanguinamento; 🇮🇹 Florence, Italy

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; 🇮🇹 Milan, Italy

Centro Emofilia e Trombosi Unità Operativa di Ematologia Ospedale San Giovanni Bosco; 🇮🇹 Napoli, Italy

Unitat Hemofilia, Hospital Vall d'Hebron; 🇪🇸 Barcellona, Spain

Centro de Hemofilia, Hospital Universitario La Paz; 🇪🇸 Madrid, Spain