Design of the INHIBIT trial: preventing inhibitors by avoiding 'danger', prolonging half-life and promoting tolerance. Issue 6 (December 2014)

• Record Type: Journal Article
• Authors: Ragni, Margaret V; Malec, Lynn M
• Is Part Of: Expert review of hematology. Volume 7:Issue 6(2014)
• Page Start: 747
• Page End: 755
• Publication Date: 2014-12
• Subjects: Hematology -- Periodicals; 616.15005
• DOI: 10.1586/17474086.2014.963550
• Languages: English
• ISSNs: 1747-4086

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>Inhibitor formation is among the most serious complications of hemophilia treatment. With the US FDA licensure of the novel long-lasting recombinant factor VIII (FVIII) Fc fusion protein, <italic>Eloctate, </italic> which prolongs FVIII half-life, we propose an innovative approach to <italic>prevent</italic> inhibitor formation. In this paper, we describe a multicenter, Phase II, single-arm, 48-week trial, the INHIBIT trial, to determine if <italic>Eloctate, </italic> begun <italic>before</italic> a bleed and continued as once weekly prophylaxis, will reduce inhibitor formation in children with hemophilia A. We <italic>hypothesize</italic> that avoiding 'danger, ' that is, immune activation by a bleed at first factor exposure and prolonging FVIII half-life will prevent inhibitors and promote FVIII-specific T-cell tolerance. If successful, this approach will suggest a new paradigm in clinical practice.</p> </abstract>