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 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

doi: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

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

Department of Clinical Medicine

98 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 language	English
Journal	Gut
Volume	64
Issue number	6
Pages (from-to)	948-956
Number of pages	9
ISSN	0017-5749
DOIs	https://doi.org/10.1136/gutjnl-2014-307498
Publication status	Published - 1 Jun 2015

Keywords

Adolescent
Adult
Aged
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination
Female
Genotype
Hepatitis C, Chronic
Humans
Imidazoles
Interferon-alpha
Male
Middle Aged
Polyethylene Glycols
Recombinant Proteins
Remission Induction
Ribavirin
Treatment Outcome
Viral Load
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1136/gutjnl-2014-307498

Cite this

Hézode, C., Hirschfield, G. M., Ghesquiere, W., Sievert, W., Rodriguez-Torres, M., Shafran, S. D., Thuluvath, P. J., Tatum, H. A., Waked, I., Esmat, G., Lawitz, E. J., Rustgi, V. K., Pol, S., Weis, N., Pockros, P. J., Bourlière, M., Serfaty, L., Vierling, J. M., Fried, M. W., ... 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

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

@article{547b2d6e58bc466c815aa9024ca6873c,

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, 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.",

keywords = "Adolescent, Adult, Aged, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Genotype, Hepatitis C, Chronic, Humans, Imidazoles, Interferon-alpha, Male, Middle Aged, Polyethylene Glycols, Recombinant Proteins, Remission Induction, Ribavirin, Treatment Outcome, Viral Load, Young Adult",

author = "Christophe H{\'e}zode and Hirschfield, {Gideon M} and Wayne Ghesquiere and William Sievert and Maribel Rodriguez-Torres and Shafran, {Stephen D} and Thuluvath, {Paul J} and Tatum, {Harvey A} and Imam Waked and Gamal Esmat and Lawitz, {Eric J} and Rustgi, {Vinod K} and Stanislas Pol and Nina Weis and Pockros, {Paul J} and Marc Bourli{\`e}re and Lawrence Serfaty and Vierling, {John M} and Fried, {Michael W} and Ola Weiland and Brunetto, {Maurizia R} and Everson, {Gregory T} and Stefan Zeuzem and Kwo, {Paul Y} and Mark Sulkowski and Norbert Br{\"a}u 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",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.",

year = "2015",

month = jun,

day = "1",

doi = "10.1136/gutjnl-2014-307498",

language = "English",

volume = "64",

pages = "948--956",

journal = "Gut",

issn = "0017-5749",

publisher = "B M J Group",

number = "6",

}

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

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Therapy, Combination

KW - Female

KW - Genotype

KW - Hepatitis C, Chronic

KW - Humans

KW - Imidazoles

KW - Interferon-alpha

KW - Male

KW - Middle Aged

KW - Polyethylene Glycols

KW - Recombinant Proteins

KW - Remission Induction

KW - Ribavirin

KW - Treatment Outcome

KW - Viral Load

KW - Young Adult

U2 - 10.1136/gutjnl-2014-307498

DO - 10.1136/gutjnl-2014-307498

M3 - Journal article

C2 - 25080450

SN - 0017-5749

VL - 64

SP - 948

EP - 956

JO - Gut

JF - Gut

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this