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

A randomised study

Christophe Hezode, Gideon M Hirschfield, Wayne G Ghesquiere, William Sievert, Maribel Rodriguez-Torres, Stephen D Shafran, Paul J Thuluvath, Harvey A Tatum, Imam A Waked, Gamal Esmat, Eric Lawitz, Vinod K Rustgi, Stanislas B Pol, Nina Weis, Paul J Pockros, Marc Bourliere, Lawrence Serfaty, John Moore Vierling, Michael W Fried, Ola Weiland & 14 others Maurizia Rossana Brunetto, Gregory T Everson, Stefan Zeuzem, Paul Y Kwo, Mark S Sulkowski, Norbert Brau, Dennis Hernandez, Fiona McPhee, Megan Wind-Rotolo, Zhaohui Liu, Stephanie Noviello, Eric A Hughes, Philip D Yin, Steven Schnittman

Research output: Contribution to journalArticleResearchpeer-review

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. © 2014 BMJ Publishing Group Ltd & British Society of Gastroenterology.

Original languageEnglish
Pages (from-to)948-956
Number of pages9
JournalGut
Volume64
Issue number6
DOIs
Publication statusPublished - 2015

Cite this

Hezode, C., Hirschfield, G. M., Ghesquiere, W. G., 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
Hezode, Christophe ; Hirschfield, Gideon M ; Ghesquiere, Wayne G ; Sievert, William ; Rodriguez-Torres, Maribel ; Shafran, Stephen D ; Thuluvath, Paul J ; Tatum, Harvey A ; Waked, Imam A ; Esmat, Gamal ; Lawitz, Eric ; Rustgi, Vinod K ; Pol, Stanislas B ; Weis, Nina ; Pockros, Paul J ; Bourliere, Marc ; Serfaty, Lawrence ; Vierling, John Moore ; Fried, Michael W ; Weiland, Ola ; Brunetto, Maurizia Rossana ; Everson, Gregory T ; Zeuzem, Stefan ; Kwo, Paul Y ; Sulkowski, Mark S ; Brau, 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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title = "Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: A randomised study",
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-RNA24) 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. {\circledC} 2014 BMJ Publishing Group Ltd & British Society of Gastroenterology.",
author = "Christophe Hezode and Hirschfield, {Gideon M} and Ghesquiere, {Wayne G} and William Sievert and Maribel Rodriguez-Torres and Shafran, {Stephen D} and Thuluvath, {Paul J} and Tatum, {Harvey A} and Waked, {Imam A} and Gamal Esmat and Eric Lawitz and Rustgi, {Vinod K} and Pol, {Stanislas B} and Nina Weis and Pockros, {Paul J} and Marc Bourliere and Lawrence Serfaty and Vierling, {John Moore} and Fried, {Michael W} and Ola Weiland and Brunetto, {Maurizia Rossana} and Everson, {Gregory T} and Stefan Zeuzem and Kwo, {Paul Y} and Sulkowski, {Mark S} and Norbert Brau and Dennis Hernandez and Fiona McPhee and Megan Wind-Rotolo and Zhaohui Liu and Stephanie Noviello and Hughes, {Eric A} and Yin, {Philip D} and Steven Schnittman",
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doi = "10.1136/gutjnl-2014-307498",
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Hezode, C, Hirschfield, GM, Ghesquiere, WG, Sievert, W, Rodriguez-Torres, M, Shafran, SD, Thuluvath, PJ, Tatum, HA, Waked, IA, Esmat, G, Lawitz, E, Rustgi, VK, Pol, SB, Weis, N, Pockros, PJ, Bourliere, M, Serfaty, L, Vierling, JM, Fried, MW, Weiland, O, Brunetto, MR, Everson, GT, Zeuzem, S, Kwo, PY, Sulkowski, MS, Brau, 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

Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection : A randomised study. / Hezode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne G; Sievert, William; Rodriguez-Torres, Maribel; Shafran, Stephen D; Thuluvath, Paul J; Tatum, Harvey A; Waked, Imam A; Esmat, Gamal; Lawitz, Eric; Rustgi, Vinod K; Pol, Stanislas B; Weis, Nina; Pockros, Paul J; Bourliere, Marc; Serfaty, Lawrence; Vierling, John Moore; Fried, Michael W; Weiland, Ola; Brunetto, Maurizia Rossana; Everson, Gregory T; Zeuzem, Stefan; Kwo, Paul Y; Sulkowski, Mark S; Brau, 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, 2015, p. 948-956.

Research output: Contribution to journalArticleResearchpeer-review

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 - Hezode, Christophe

AU - Hirschfield, Gideon M

AU - Ghesquiere, Wayne G

AU - Sievert, William

AU - Rodriguez-Torres, Maribel

AU - Shafran, Stephen D

AU - Thuluvath, Paul J

AU - Tatum, Harvey A

AU - Waked, Imam A

AU - Esmat, Gamal

AU - Lawitz, Eric

AU - Rustgi, Vinod K

AU - Pol, Stanislas B

AU - Weis, Nina

AU - Pockros, Paul J

AU - Bourliere, Marc

AU - Serfaty, Lawrence

AU - Vierling, John Moore

AU - Fried, Michael W

AU - Weiland, Ola

AU - Brunetto, Maurizia Rossana

AU - Everson, Gregory T

AU - Zeuzem, Stefan

AU - Kwo, Paul Y

AU - Sulkowski, Mark S

AU - Brau, 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

Y1 - 2015

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, 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-RNA24) 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. © 2014 BMJ Publishing Group Ltd & British Society of Gastroenterology.

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, 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-RNA24) 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. © 2014 BMJ Publishing Group Ltd & British Society of Gastroenterology.

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U2 - 10.1136/gutjnl-2014-307498

DO - 10.1136/gutjnl-2014-307498

M3 - Article

VL - 64

SP - 948

EP - 956

JO - Gut

JF - Gut

SN - 0017-5749

IS - 6

ER -