Randomized study of asunaprevir plus pegylated interferon-α and ribavirin for previously untreated genotype 1 chronic hepatitis C

Academic Article

Abstract

  • Background: Asunaprevir is a selective NS3 protease inhibitor with in vitro activity against HCV genotypes 1 and 4. Methods: In this Phase IIa double-blind study, treatmentnaive HCV genotype-1-infected patients in the United States and France were randomly assigned 1:1:1:1 to placebo or asunaprevir 200 mg twice daily, 600 mg twice daily or 600 mg once daily in combination with pegylated interferon (PEG-IFN)-α2a and ribavirin for 48 weeks. The primary eficacy end point was undetectable HCV RNA at weeks 4 and 12 (extended rapid virological response [eRVR]). Other end points included safety and undetectable HCV RNA at 24 weeks post-treatment (24-week sustained virological response [SVR 24]). Results: A total of 47 patients were randomized and treated. eRVR was achieved by 75% (9/12), 75% (9/12) and 92% (11/12) of patients in the asunaprevir 200 mg twice-daily, 600 mg twice-daily and 600 mg once-daily groups, respectively, versus 0% (0/11) in the placebo group. Corresponding SVR 24 rates were 83% (10/12), 83% (10/12) and 92% (11/12) in the asunaprevir groups and 46% (5/11) in the placebo group. There was no virological breakthrough in any asunaprevir group. Following the 12-week analysis, the 600 mg doses were reduced to 200 mg twice daily because of a greater frequency of transaminase elevations at the 600 mg dose. The most common grade 3-4 laboratory abnormalities were consistent with those reported for PEG-IFN and ribavirin. Conclusions: Asunaprevir plus PEG-IFN and ribavirin achieved higher response rates than placebo plus PEG-IFN and ribavirin, with a tolerable adverse event proile at the 200 mg twice-daily dose. This dose is being evaluated in the Phase IIb and Phase III studies. © 2013 International Medical Press.
  • Authors

    Published In

  • Antiviral Therapy  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bronowicki JP; Pol S; Thuluvath PJ; Larrey D; Martorell CT; Rustgi VK; Morris DW; Younes Z; Fried MW; Bourlière M
  • Start Page

  • 885
  • End Page

  • 893
  • Volume

  • 18
  • Issue

  • 7