Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: A randomised study

Christophe Hezode, Gideon M Hirschfield, Wayne G Ghesquiere, William Sievert, Maribel Rodriguez-Torres, Stephen D Shafran, Paul J Thuluvath, Harvey A Tatum, Imam A Waked, Gamal Esmat, Eric Lawitz, Vinod K Rustgi, Stanislas B Pol, Nina Weis, Paul J Pockros, Marc Bourliere, Lawrence Serfaty, John Moore Vierling, Michael W Fried, Ola WeilandMaurizia Rossana Brunetto, Gregory T Everson, Stefan Zeuzem, Paul Y Kwo, Mark S Sulkowski, Norbert Brau, Dennis Hernandez, Fiona McPhee, Megan Wind-Rotolo, Zhaohui Liu, Stephanie Noviello, Eric A Hughes, Philip D Yin, Steven Schnittman

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Abstract

Objective To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. Design In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA<lower limit of quantitation at Week 4 and undetectable at Week 10) were rerandomised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 (extended rapid virologic response, eRVR) and at 24 weeks post-treatment (sustained virologic response, SVR24) among genotype 1-infected patients. Results Overall, eRVR was achieved by 54.4% (80/147) of genotype 1-infected patients receiving daclatasvir 20 mg, 54.1% (79/146) receiving 60 mg versus 13.9% (10/72) receiving placebo. SVR24 was achieved among 87 (59.2%), 87 (59.6%), and 27 (37.5%) patients in these groups, respectively. Higher proportions of genotype 4-infected patients receiving daclatasvir 20 mg (66.7%; 8/12) or 60 mg (100.0%; 12/12) achieved SVR24 versus placebo (50.0%; 3/6). A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration. Adverse events occurred with similar frequency across all treatment groups. Conclusions The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4. © 2014 BMJ Publishing Group Ltd & British Society of Gastroenterology.

Original languageEnglish
Pages (from-to)948-956
Number of pages9
JournalGut
Volume64
Issue number6
DOIs
Publication statusPublished - 2015

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