Viral kinetic models of HCV clearance in hemophiliacs treated with telaprevir

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DESCRIPTION (provided by applicant): Infection with the hepatitis C virus is an important contributor to morbidity and mortality among those with hemophilia and other inherited bleeding disorders in whom such infections are common. Current treatment modalities using pegylated-interferon alfa and ribavirin are suboptimal in terms of response. New small molecules targeted to inhibition of HCV replication offer promise in terms of improved response rates, and shorter durations of therapy, but their use has not been assessed in special populations, including those with hemophilia and related disorders. Furthermore, the optimal regimen which provides high efficacy with low levels of development of viral resistance to the experimental agent has not been established. This pilot study will examine the efficacy and safety of two strategies utilizing telaprevir in combination with pegylated- interferon alfa/ribavirin. Using powerful mathematical modeling techniques we will explore first and second phase kinetic responses to treatment in patients with inherited bleeding disorders who are either treatment na¿ve or treatment experienced (interferon-based HCV treatment). Specifically our aims are 1: Development and implementation of a pilot clinical trial designed to assess dynamic kinetic response parameters and safety of telaprevir combined with standard of care therapy in subjects with inherited bleeding disorders, and 2: To evaluate prevalence and rate of emergence of class-specific resistance mutations to protease inhibitors and to identify early predictors of mutational selection. This study will inform development of a large, multicenter trial that would follow completion of the pilot phase proposed herein.