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

Jean Pierre Bronowicki, Stanislas Pol, Paul J. Thuluvath, Dominique Larrey, Claudia T. Martorell, Vinod K. Rustgi, David W. Morris, Ziad Younes, Michael W. Fried, Marc Bourlière, Christophe Hézode, K. Rajender Reddy, Omar Massoud, Gary A. Abrams, Vlad Ratziu, Bing He, Timothy Eley, Alaa Ahmad, David Cohen, Robert HindesFiona McPhee, Bridget Reilly, Patricia Mendez, Eric Hughes

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)885-893
Number of pages9
JournalAntiviral Therapy
Volume18
Issue number7
DOIs
StatePublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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