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Clinical Trial
. 2014 Dec;7(6):747-55.
doi: 10.1586/17474086.2014.963550. Epub 2014 Nov 5.

Design of the INHIBIT trial: preventing inhibitors by avoiding 'danger', prolonging half-life and promoting tolerance

Margaret V Ragni  1 , Lynn M Malec
Affiliations
Clinical Trial

Design of the INHIBIT trial: preventing inhibitors by avoiding 'danger', prolonging half-life and promoting tolerance

Margaret V Ragni et al. Expert Rev Hematol. 2014 Dec.

Abstract

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.

Keywords: Tregs; coagulation factor VIII; hemophilia A; inhibitor formation; long-lasting factor VIII; tolerance.

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Conflict of interest statement

Financial & competing interests disclosure: MV Ragni receives research funding from Baxter Bioscience, Bayer, Biogen Idec, CSL Behring, Merck, Novartis, Novo-Nordisk, SPARK and Vascular Medicine Institute. LM Malec has received research funding from Baxter Bioscience. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1
Figure 1
Schema for the Hemophilia INHIBIT Trial.
See this image and copyright information in PMC

References

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