TY - JOUR
T1 - Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection
T2 - A randomised study
AU - Hézode, Christophe
AU - Hirschfield, Gideon M.
AU - Ghesquiere, Wayne
AU - Sievert, William
AU - Rodriguez-Torres, Maribel
AU - Shafran, Stephen D.
AU - Thuluvath, Paul J.
AU - Tatum, Harvey A.
AU - Waked, Imam
AU - Esmat, Gamal
AU - Lawitz, Eric J.
AU - Rustgi, Vinod K.
AU - Pol, Stanislas
AU - Weis, Nina
AU - Pockros, Paul J.
AU - Bourlière, Marc
AU - Serfaty, Lawrence
AU - Vierling, John M.
AU - Fried, Michael W.
AU - Weiland, Ola
AU - Brunetto, Maurizia R.
AU - Everson, Gregory T.
AU - Zeuzem, Stefan
AU - Kwo, Paul Y.
AU - Sulkowski, Mark
AU - Bräu, Norbert
AU - Hernandez, Dennis
AU - McPhee, Fiona
AU - Wind-Rotolo, Megan
AU - Liu, Zhaohui
AU - Noviello, Stephanie
AU - Hughes, Eric A.
AU - Yin, Philip D.
AU - Schnittman, Steven
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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, placebocontrolled 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 peginterferonalfa: 2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCVRNA< 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.
AB - 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, placebocontrolled 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 peginterferonalfa: 2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCVRNA< 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.
UR - https://www.scopus.com/pages/publications/84932619401
UR - https://www.scopus.com/pages/publications/84932619401#tab=citedBy
U2 - 10.1136/gutjnl-2014-307498
DO - 10.1136/gutjnl-2014-307498
M3 - Article
C2 - 25080450
AN - SCOPUS:84932619401
SN - 0017-5749
VL - 64
SP - 948
EP - 956
JO - Gut
JF - Gut
IS - 6
ER -