NCT02479087

Safety/Efficacy Study to Assess Whether FVIII/VWF Concentrate Can Induce Immune Tolerance in Haemophilia A Patients

IMMUNE TOLERANCE INDUCTION, BY FACTOR VIII CONCENTRATE CONTAINING VON WILLEBRAND FACTOR, IN SEVERE OR MODERATE HAEMOPHILIA A PATIENTS WITH INHIBITORS

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Academic / Other
• Sex: Male
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the role of a FVIII/VWF complex concentrate (Emoclot) in successfully inducing immune tolerance (I.T.I.) in patients with Haemophilia A with inhibitors, including patients at high risk of failure.

Detailed description

The development of factor VIII inhibitors occurs in approximately 30 to 40% of patients with severe Haemophilia A. The main negative clinical and cost consequence is the ineffectiveness of replacement therapy in patients with high-titer antibodies, who have a shorter life and greater morbidity than those who do not develop inhibitors. It is known from immunology that a regular and frequent exposure to the antigen of FVIII can induce tolerance of the immune system of the patient with inhibitors. This effect, called "immune tolerance induction" (ITI) is usually achieved after a prolonged exposure of the patient to FVIII, and is a common way of managing the condition of patients with inhibitors as well as the treatment of bleeding episodes with large amounts of hemostatic agents. In vitro and retrospective clinical studies suggest that FVIII/VWF complex concentrates may have less immunogenicity with respect to those plasma-derived concentrates purified with monoclonal antibodies (MABs), and recombinant DNA factor VIII concentrates (rFVIII), in both which the von Willebrand factor (VWF) is absent. Immune tolerance induction (ITI) showed to be effective in about 70% of Haemophiliacs with inhibitors. Poor prognosis factors have been identified by different registries: age ≥ 6 years, ITI started \>1 year from inhibitor development, inhibitor peaks \>200 BU, inhibitor titer \>10 BU at the start of ITI and previously failed ITI. The results of clinical studies suggest that complex concentrates of VWF/FVIII can be effective in ITI, even in patients at high risk of failure. To explain these findings, a role for VWF (i.e. prolonged antigen exposure) has been hypothesized.

Conditions

• Hemophilia A

Interventions

Type	Name	Description
DRUG	Plasma-derived FVIII/VWF concentrate	The investigational treatment is with lyophilized plasma-derived Factor VIII. The product belongs to the factor VIII concentrates class, containing also VW Factor in an average ratio VW/VIII of \> 1: 4.5. The product is as a powder and a solvent solution for continuous infusion of Factor VIII. The specific activity of Factor VIII is of approximately 80 IU/mg protein. The number of units of FVIII administered is expressed in International Units (IU), which are consistent with current WHO standards for products containing Factor VIII. The activity of Factor VIII in plasma is expressed either as a percentage (compared to normal human plasma) or in International Units (compared to the international standard for FVIII in plasma).

Timeline

• Start date: 2015-01-01
• Primary completion: 2019-01-01
• Completion: 2020-01-01
• First posted: 2015-06-23
• Last updated: 2015-06-23

Locations

4 sites across 2 countries: Egypt, India