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Abstract Details
Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study
Author information
1Hôpital Henri Mondor, AP-HP, Université Paris-Est, Inserm U955, Créteil, France.
2Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.
3Vancouver Island Health Authority & University of British Columbia, Victoria, British Columbia, Canada.
4Monash University and Monash Health, Melbourne, Australia.
5Fundacion De Investigacion, San Juan Bautista School of Medicine, San Juan, Puerto Rico.
6University of Alberta Hospital, Edmonton, Canada.
7Mercy Medical Center, Baltimore, Maryland, USA.
8Options Health Research, LLC, Tulsa, Oklahoma, USA.
9National Liver Institute, Shebin Elkom, Egypt.
10Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
11Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA.
12Metropolitan Research, Fairfax, Virginia, USA.
13Inserm U1016 and Liver Unit, Université Paris Descartes, Hôpital Cochin, Paris, France.
14Copenhagen University Hospital, Hvidovre, Denmark.
15Scripps Clinic, La Jolla, California, USA.
16Hôpital Saint Joseph, Marseille, France.
17Hôpital Saint-Antoine, Paris, France.
18Baylor College of Medicine, Houston, Texas, USA.
19University of North Carolina, Chapel Hill, North Carolina, USA.
20Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
21Hepatology Unit, University Hospital of Pisa, Pisa, Italy.
22University of Colorado Denver, Aurora, Colorado, USA.
23Goethe University, Frankfurt, Germany.
24Indiana University, Indianapolis, Indiana, USA.
25Johns Hopkins University, Baltimore, Maryland, USA.
26James J. Peters VA Medical Center, Bronx, New York, USA.
27Bristol-Myers Squibb, Clinical Research and Development, Wallingford, Connecticut, USA.
28Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
29Bristol-Myers Squibb Research and Development, Hopewell, New Jersey, USA.
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
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.
TRIAL REGISTRATION NUMBER:
NCT01125189.