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Region Hovedstaden - en del af Københavns Universitetshospital
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Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  • Christophe Hézode
  • Gideon M Hirschfield
  • Wayne Ghesquiere
  • William Sievert
  • Maribel Rodriguez-Torres
  • Stephen D Shafran
  • Paul J Thuluvath
  • Harvey A Tatum
  • Imam Waked
  • Gamal Esmat
  • Eric J Lawitz
  • Vinod K Rustgi
  • Stanislas Pol
  • Nina Weis
  • Paul J Pockros
  • Marc Bourlière
  • Lawrence Serfaty
  • John M Vierling
  • Michael W Fried
  • Ola Weiland
  • Maurizia R Brunetto
  • Gregory T Everson
  • Stefan Zeuzem
  • Paul Y Kwo
  • Mark Sulkowski
  • Norbert Bräu
  • Dennis Hernandez
  • Fiona McPhee
  • Megan Wind-Rotolo
  • Zhaohui Liu
  • Stephanie Noviello
  • Eric A Hughes
  • Philip D Yin
  • Steven Schnittman
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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.

OriginalsprogEngelsk
TidsskriftGut
Vol/bind64
Sider (fra-til)948-956
Antal sider8
ISSN0017-5749
DOI
StatusUdgivet - 2015

ID: 44865560