Clinical trial NCT01105546: rFVIIa Prophylaxis in Children With Hemophilia A and Inhibitors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hemophilia A With Inhibitors
Keywords: hemophilia A
inhibitors
prophylaxis
immune tolerance induction
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2010-04-16
Enrollment: 50
Sex: MALE
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total number of joint bleeds.
timeFrame: 18 months
Secondary outcomes:
measure: Joint status evaluated by the Hemophilia Joint Health Score
timeFrame: 18 months
measure: Number of adverse events and serious adverse events.
timeFrame: 18 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Lyon
country: France
facility: Haemophilia Comprehensive Care Centre, Edouard Herriot University Hospital
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain Haemophilia Care Center, Medical Center
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte, Prof.-Hess-Kinderklinik
city: Frankfurt/M
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitat
city: Florence
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi Agenzia per l'emofilia e Centro di riferimento regionale per i disordini congeniti del sanguinamento
city: Milan
country: Italy
facility: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: Centro Emofilia e Trombosi Unità Operativa di Ematologia Ospedale San Giovanni Bosco
city: Bucarest
country: Romania
facility: National Institute for Transfusional Hematology
city: Timisoara
country: Romania
facility: Spitaluc Clinic de Urgenta pentru Copii Louis Turcanu, University of Medicine and Pharmacy
city: Barcellona
country: Spain
facility: Unitat Hemofilia, Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Centro de Hemofilia, Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Unidad de Coagulopatias Congenitas, Hospital Universitario la Fe
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Elena Santagostino, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: