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Gastroenterology. 2015 Feb;148(2):355-366.e1. doi: 10.1053/j.gastro.2014.10.007. Epub 2014 Oct 13.

Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection.

Author information

  • 1Kirby Institute, University of New South Wales and St Vincent's Hospital, Sydney, Australia. Electronic address: gdore@kirby.unsw.edu.au.
  • 2The Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas.
  • 3Department of Hepatology, Hôpital Henri Mondor, Créteil, France.
  • 4Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada.
  • 5Department of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada.
  • 6Options Health Research, Tulsa, Oklahoma.
  • 7Department of Clinical Medicine, Sapienza Università di Roma, Rome, Italy.
  • 8Faculty of Medicine, Hôpital De L'Archet 2, Nice, France.
  • 9Hepatology Unit, University Hospital, Pisa, Italy.
  • 10University Division of Infectious and Tropical Diseases, Azienda Ospedaliera Spedali Civili, Brescia, Italy.
  • 11AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
  • 12Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
  • 13Vancouver Island Health Authority and University of British Columbia, Victoria, British Columbia, Canada.
  • 14Liver Unit, University of Calgary, Calgary, Alberta, Canada.
  • 15Département d'Hépato-Gastroentérologie et Transplantation, Hôpital Saint Eloi, Montpellier, France.
  • 16Université Paris Descartes, Unité d'Hépatologie, Hôpital Cochin, Paris, France.
  • 17Department of Gastroenterology and Hepatology, Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia.
  • 18Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Sydney, Australia.
  • 19Divisions of Gastroenterology and General Internal Medicine, Toronto General Hospital, Toronto, Ontario, Canada.
  • 20Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, Pessac, France.
  • 21Research and Development, Bristol-Myers Squibb, Braine-l'Alleud, Belgium.
  • 22Research and Development, Bristol-Myers Squibb, Wallingford, Connecticut.
  • 23Research and Development, Bristol-Myers Squibb, Princeton, New Jersey.

Abstract

BACKGROUND & AIMS:

Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy.

METHODS:

Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24).

RESULTS:

Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy.

CONCLUSIONS:

Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Antiviral; Combination Therapy; DAA; NS5A Replication Complex Inhibitor

PMID:
25311593
[PubMed - indexed for MEDLINE]
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