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Randomized trial of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 or 4 chronic hepatitis C

Abstract : Background & Aims Asunaprevir is a selective HCV NS3 protease inhibitor, active against genotypes 1, 4, 5, and 6 in vitro. We evaluated asunaprevir plus peginterferon alfa-2a/ribavirin (PegIFNα/RBV) for genotype 1 and 4 chronic HCV. Methods In this phase 2b, double-blind, placebo-controlled study, treatment-naive adults with genotype 1 (n = 213) or 4 (n = 25) were randomly assigned (3:1) to asunaprevir 200 mg or placebo twice daily plus PegIFNα/RBV. Asunaprevir recipients, achieving protocol-defined response (HCV-RNA below quantification limit at week 4 and undetectable at week 10), were rerandomized at week 12 to continue asunaprevir-based triple therapy or receive placebo plus PegIFNα/RBV for weeks 13–24. Patients without protocol-defined response (PDR) and placebo recipients continued PegIFNα/RBV through week 48. Co-primary end points were undetectable HCV-RNA at week 4 and 12 (eRVR) and 24 weeks posttreatment (SVR24). Results Most patients were male (64.3%), white (83.6%), and had non-CC IL28B genotypes (71.3%). Among genotype 1 patients, eRVR rates (asunaprevir vs. placebo) were 67% (80% CI 62, 72) vs. 6% (80% CI 2, 10); corresponding SVR24 rates were 64% (80% CI 59, 68) vs. 44% (80% CI 36, 53). SVR24 among genotype 4 patients was 89% (asunaprevir) vs. 43% (placebo). Rates of rash and haematologic adverse events were similar between treatment groups. Five asunaprevir-treated patients had grade 4 alanine aminotransferase elevations that resolved following discontinuation (n = 4) or with continued dosing (n = 1). Conclusions Addition of asunaprevir to PegIFNα/RBV in treatment-naive genotype 1- or 4-infected patients improves response rates and is well tolerated, with aminotransferase elevations that were manageable with appropriate monitoring.
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https://hal.univ-lorraine.fr/hal-01699241
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Submitted on : Friday, February 2, 2018 - 10:45:43 AM
Last modification on : Friday, December 11, 2020 - 3:18:48 AM

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Jean-Pierre Bronowicki, Vlad Ratziu, Adrian Gadano, Paul Thuluvath, Fernando Bessone, et al.. Randomized trial of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 or 4 chronic hepatitis C. Journal of Hepatology, Elsevier, 2014, 61 (6), pp.1220 - 1227. ⟨10.1016/j.jhep.2014.07.011⟩. ⟨hal-01699241⟩

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