Design of the INHIBIT trial: preventing inhibitors by avoiding 'danger', prolonging half-life and promoting tolerance. Expert Rev Hematol 2014 Dec;7(6):747-55
Date
11/07/2014Pubmed ID
25374055Pubmed Central ID
PMC4356531DOI
10.1586/17474086.2014.963550Scopus ID
2-s2.0-84911430479 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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, Eloctate, which prolongs FVIII half-life, we propose an innovative approach to prevent inhibitor formation. In this paper, we describe a multicenter, Phase II, single-arm, 48-week trial, the INHIBIT trial, to determine if Eloctate, begun before a bleed and continued as once weekly prophylaxis, will reduce inhibitor formation in children with hemophilia A. We hypothesize 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.
Author List
Ragni MV, Malec LMMESH terms used to index this publication - Major topics in bold
ChildChild, Preschool
Factor VIII
Half-Life
Hemophilia A
Humans
Immune Tolerance
Immunity, Cellular
Immunoglobulin Fc Fragments
Recombinant Fusion Proteins
T-Lymphocytes
