Potentially, this strategy would increase the SVR rate and protect against the emergence of viral resistance.

Avoiding interferon and ribavirin also would improve tolerability, perhaps increasing compliance, resulting in more effective therapy. The study presented here describes outcomes from 12 or 24 weeks of treatment with an interferon-free, Protein Tyrosine Kinase inhibitor ribavirin-free combination of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV GT 1 infection. This open-label, randomized, phase 2a study recruited patients from 13 centers in the United States and France. Patients were enrolled and completed treatment from November 17, 2011, to March 5, 2013. The study was approved by appropriate institutional review boards and/or independent ethics committees, and was performed in accordance with the Declaration of Helsinki and Good Clinical Practice as defined by the International Conference on Harmonization and ethical principles of local regulatory requirements. All patients provided written informed consent. All authors had access to the study data and reviewed and approved the final manuscript. Inclusion criteria selleck inhibitor were age 18-70 years, chronic HCV GT 1 infection with RNA level of 105 IU/mL or greater, no previous HCV therapy (treatment-naive), and no evidence of cirrhosis (as documented

by markers of cirrhosis, FibroTest [BioPredictive, Paris, France] score <0.72 and aspartate aminotransferase:platelet ratio <2, or liver biopsy). Patients with a FibroTest or aspartate aminotransferase:platelet ratio score exceeding the threshold for study

inclusion were required to have a liver biopsy documenting the absence of cirrhosis. METAVIR category for each patient was derived from the FibroTest result based on the conversion on the manufacturer’s website. Exclusion criteria included Sitaxentan an alanine aminotransferase level that was 5× or more the upper limit of normal, total bilirubin level of 2 mg/dL or greater, direct bilirubin level greater than the upper limit of normal, international normalized ratio of 1.7 or greater, albumin level of 3.2 g/dL or less, hemoglobin level less than 11 g/dL for women and less than 12 g/dL for men, absolute neutrophil count less than 1.5 × 109 cells/L (or <1.2 × 109 cells/L for African American individuals), platelet count less than 90 × 109 cells/L, creatinine clearance less than 50 mL/min, and ineligibility for peginterferon alfa 2a or ribavirin if needed for treatment intensification (see later). Women of child-bearing potential were required to use at least 2 contraception methods. All randomized patients received daclatasvir (60 mg, orally, once daily), asunaprevir (200 mg, orally, twice daily), and BMS-791325 orally at either 75 or 150 mg twice daily. The dose selection of BMS-791325 was based on phase 1 antiviral activity and safety.