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

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 WeilandMaurizia 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

Research output: Contribution to journalArticle

89 Citations (Scopus)

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, 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.

Original languageEnglish (US)
Pages (from-to)948-956
Number of pages9
JournalGut
Volume64
Issue number6
DOIs
StatePublished - Jun 1 2015

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Ribavirin
Chronic Hepatitis C
Genotype
Placebos
Infection
Therapeutics
BMS-790052
Double-Blind Method
RNA
Safety

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Hézode, C., Hirschfield, G. M., Ghesquiere, W., Sievert, W., Rodriguez-Torres, M., Shafran, S. D., ... Schnittman, S. (2015). Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: A randomised study. Gut, 64(6), 948-956. https://doi.org/10.1136/gutjnl-2014-307498

Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection : A randomised study. / Hézode, Christophe; Hirschfield, Gideon M.; Ghesquiere, Wayne; Sievert, William; Rodriguez-Torres, Maribel; Shafran, Stephen D.; Thuluvath, Paul J.; Tatum, Harvey A.; Waked, Imam; Esmat, Gamal; Lawitz, Eric J.; Rustgi, Vinod K.; Pol, Stanislas; Weis, Nina; Pockros, Paul J.; Bourlière, Marc; Serfaty, Lawrence; Vierling, John M.; Fried, Michael W.; Weiland, Ola; Brunetto, Maurizia R.; Everson, Gregory T.; Zeuzem, Stefan; Kwo, Paul Y.; Sulkowski, Mark; Bräu, Norbert; Hernandez, Dennis; McPhee, Fiona; Wind-Rotolo, Megan; Liu, Zhaohui; Noviello, Stephanie; Hughes, Eric A.; Yin, Philip D.; Schnittman, Steven.

In: Gut, Vol. 64, No. 6, 01.06.2015, p. 948-956.

Research output: Contribution to journalArticle

Hézode, C, Hirschfield, GM, Ghesquiere, W, Sievert, W, Rodriguez-Torres, M, Shafran, SD, Thuluvath, PJ, Tatum, HA, Waked, I, Esmat, G, Lawitz, EJ, Rustgi, VK, Pol, S, Weis, N, Pockros, PJ, Bourlière, M, Serfaty, L, Vierling, JM, Fried, MW, Weiland, O, Brunetto, MR, Everson, GT, Zeuzem, S, Kwo, PY, Sulkowski, M, Bräu, N, Hernandez, D, McPhee, F, Wind-Rotolo, M, Liu, Z, Noviello, S, Hughes, EA, Yin, PD & Schnittman, S 2015, 'Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: A randomised study', Gut, vol. 64, no. 6, pp. 948-956. https://doi.org/10.1136/gutjnl-2014-307498
Hézode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, Shafran SD et al. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: A randomised study. Gut. 2015 Jun 1;64(6):948-956. https://doi.org/10.1136/gutjnl-2014-307498
Hézode, Christophe ; Hirschfield, Gideon M. ; Ghesquiere, Wayne ; Sievert, William ; Rodriguez-Torres, Maribel ; Shafran, Stephen D. ; Thuluvath, Paul J. ; Tatum, Harvey A. ; Waked, Imam ; Esmat, Gamal ; Lawitz, Eric J. ; Rustgi, Vinod K. ; Pol, Stanislas ; Weis, Nina ; Pockros, Paul J. ; Bourlière, Marc ; Serfaty, Lawrence ; Vierling, John M. ; Fried, Michael W. ; Weiland, Ola ; Brunetto, Maurizia R. ; Everson, Gregory T. ; Zeuzem, Stefan ; Kwo, Paul Y. ; Sulkowski, Mark ; Bräu, Norbert ; Hernandez, Dennis ; McPhee, Fiona ; Wind-Rotolo, Megan ; Liu, Zhaohui ; Noviello, Stephanie ; Hughes, Eric A. ; Yin, Philip D. ; Schnittman, Steven. / Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection : A randomised study. In: Gut. 2015 ; Vol. 64, No. 6. pp. 948-956.
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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, 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; HCVRNA24) 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.",
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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; HCVRNA24) 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; HCVRNA24) 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.

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