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Gut. 2015 Jun;64(6):948-56. doi: 10.1136/gutjnl-2014-307498. Epub 2014 Jul 30.

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

Author information

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

TRIAL REGISTRATION NUMBER:

NCT01125189.

PMID:
25080450
DOI:
10.1136/gutjnl-2014-307498
[Indexed for MEDLINE]

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