Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection

Stefan Zeuzem, Christophe Hézode, Jean Pierre Bronowicki, Veronique Loustaud-Ratti, Francisco Gea, Maria Buti, Antonio Olveira, Tivadar Banyai, M. Tarek Al-Assi, Joerg Petersen, Dominique Thabut, Adrian Gadano, Ronald Pruitt, Mihály Makara, Marc Bourlière, Stanislas Pol, Maria Beumont-Mauviel, Sivi Ouwerkerk-Mahadevan, Gaston Picchio, Marc Bifano & 5 others Fiona Mcphee, Navdeep Boparai, Kin Cheung, Eric A. Hughes, Stephanie Noviello

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    Background & Aims We evaluated the combination of daclatasvir (pan-genotypic NS5A inhibitor) and simeprevir (NS3/4A protease inhibitor), with or without ribavirin, in hepatitis C virus genotype 1-infected patients. Methods This phase II, open-label study enrolled treatment-naive patients or prior null responders with genotype 1b (n = 147) or 1a (n = 21) infection. Genotype 1b-infected patients were randomized 1:1 to receive daclatasvir 30 mg plus simeprevir 150 mg once daily with or without ribavirin; those who completed the initial 12-week treatment were re-randomized 1:1 to stop treatment or continue treatment through to week 24. Genotype 1a-infected patients received daclatasvir plus simeprevir with ribavirin for 24 weeks. The primary endpoint was the proportion of patients with sustained virologic response at posttreatment week 12 (SVR12). Results For genotype 1b, 84.9% (45/53) and 74.5% (38/51) of treatment-naive patients and 69.6% (16/23) and 95.0% (19/20) of prior null responders to peginterferon and ribavirin achieved SVR12 with daclatasvir plus simeprevir alone and with ribavirin, respectively. Treatment duration did not have a well-defined impact on response. For genotype 1a, daclatasvir plus simeprevir with ribavirin provided a 66.7% (8/12) response rate in treatment-naive patients and was not effective in prior null responders. Data suggest that baseline resistance polymorphisms influenced SVR12 rates. Daclatasvir plus simeprevir was well tolerated with or without ribavirin with low incidences of serious adverse events and adverse events leading to discontinuation. Conclusions Daclatasvir plus simeprevir, with or without ribavirin, was effective with a 12- or 24-week duration in genotype 1b-infected patients and was well tolerated. ClinicalTrials.gov identifier: NCT01628692.

    Original languageEnglish (US)
    Pages (from-to)292-300
    Number of pages9
    JournalJournal of Hepatology
    Volume64
    Issue number2
    DOIs
    StatePublished - Feb 1 2016

    Fingerprint

    Ribavirin
    Chronic Hepatitis C
    Hepacivirus
    Genotype
    Infection
    Therapeutics
    Simeprevir
    BMS-790052
    Protease Inhibitors
    Incidence

    All Science Journal Classification (ASJC) codes

    • Hepatology

    Cite this

    Zeuzem, S., Hézode, C., Bronowicki, J. P., Loustaud-Ratti, V., Gea, F., Buti, M., ... Noviello, S. (2016). Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection. Journal of Hepatology, 64(2), 292-300. https://doi.org/10.1016/j.jhep.2015.09.024

    Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection. / Zeuzem, Stefan; Hézode, Christophe; Bronowicki, Jean Pierre; Loustaud-Ratti, Veronique; Gea, Francisco; Buti, Maria; Olveira, Antonio; Banyai, Tivadar; Al-Assi, M. Tarek; Petersen, Joerg; Thabut, Dominique; Gadano, Adrian; Pruitt, Ronald; Makara, Mihály; Bourlière, Marc; Pol, Stanislas; Beumont-Mauviel, Maria; Ouwerkerk-Mahadevan, Sivi; Picchio, Gaston; Bifano, Marc; Mcphee, Fiona; Boparai, Navdeep; Cheung, Kin; Hughes, Eric A.; Noviello, Stephanie.

    In: Journal of Hepatology, Vol. 64, No. 2, 01.02.2016, p. 292-300.

    Research output: Contribution to journalArticle

    Zeuzem, S, Hézode, C, Bronowicki, JP, Loustaud-Ratti, V, Gea, F, Buti, M, Olveira, A, Banyai, T, Al-Assi, MT, Petersen, J, Thabut, D, Gadano, A, Pruitt, R, Makara, M, Bourlière, M, Pol, S, Beumont-Mauviel, M, Ouwerkerk-Mahadevan, S, Picchio, G, Bifano, M, Mcphee, F, Boparai, N, Cheung, K, Hughes, EA & Noviello, S 2016, 'Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection', Journal of Hepatology, vol. 64, no. 2, pp. 292-300. https://doi.org/10.1016/j.jhep.2015.09.024
    Zeuzem, Stefan ; Hézode, Christophe ; Bronowicki, Jean Pierre ; Loustaud-Ratti, Veronique ; Gea, Francisco ; Buti, Maria ; Olveira, Antonio ; Banyai, Tivadar ; Al-Assi, M. Tarek ; Petersen, Joerg ; Thabut, Dominique ; Gadano, Adrian ; Pruitt, Ronald ; Makara, Mihály ; Bourlière, Marc ; Pol, Stanislas ; Beumont-Mauviel, Maria ; Ouwerkerk-Mahadevan, Sivi ; Picchio, Gaston ; Bifano, Marc ; Mcphee, Fiona ; Boparai, Navdeep ; Cheung, Kin ; Hughes, Eric A. ; Noviello, Stephanie. / Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection. In: Journal of Hepatology. 2016 ; Vol. 64, No. 2. pp. 292-300.
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    abstract = "Background & Aims We evaluated the combination of daclatasvir (pan-genotypic NS5A inhibitor) and simeprevir (NS3/4A protease inhibitor), with or without ribavirin, in hepatitis C virus genotype 1-infected patients. Methods This phase II, open-label study enrolled treatment-naive patients or prior null responders with genotype 1b (n = 147) or 1a (n = 21) infection. Genotype 1b-infected patients were randomized 1:1 to receive daclatasvir 30 mg plus simeprevir 150 mg once daily with or without ribavirin; those who completed the initial 12-week treatment were re-randomized 1:1 to stop treatment or continue treatment through to week 24. Genotype 1a-infected patients received daclatasvir plus simeprevir with ribavirin for 24 weeks. The primary endpoint was the proportion of patients with sustained virologic response at posttreatment week 12 (SVR12). Results For genotype 1b, 84.9{\%} (45/53) and 74.5{\%} (38/51) of treatment-naive patients and 69.6{\%} (16/23) and 95.0{\%} (19/20) of prior null responders to peginterferon and ribavirin achieved SVR12 with daclatasvir plus simeprevir alone and with ribavirin, respectively. Treatment duration did not have a well-defined impact on response. For genotype 1a, daclatasvir plus simeprevir with ribavirin provided a 66.7{\%} (8/12) response rate in treatment-naive patients and was not effective in prior null responders. Data suggest that baseline resistance polymorphisms influenced SVR12 rates. Daclatasvir plus simeprevir was well tolerated with or without ribavirin with low incidences of serious adverse events and adverse events leading to discontinuation. Conclusions Daclatasvir plus simeprevir, with or without ribavirin, was effective with a 12- or 24-week duration in genotype 1b-infected patients and was well tolerated. ClinicalTrials.gov identifier: NCT01628692.",
    author = "Stefan Zeuzem and Christophe H{\'e}zode and Bronowicki, {Jean Pierre} and Veronique Loustaud-Ratti and Francisco Gea and Maria Buti and Antonio Olveira and Tivadar Banyai and Al-Assi, {M. Tarek} and Joerg Petersen and Dominique Thabut and Adrian Gadano and Ronald Pruitt and Mih{\'a}ly Makara and Marc Bourli{\`e}re and Stanislas Pol and Maria Beumont-Mauviel and Sivi Ouwerkerk-Mahadevan and Gaston Picchio and Marc Bifano and Fiona Mcphee and Navdeep Boparai and Kin Cheung and Hughes, {Eric A.} and Stephanie Noviello",
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    T1 - Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection

    AU - Zeuzem, Stefan

    AU - Hézode, Christophe

    AU - Bronowicki, Jean Pierre

    AU - Loustaud-Ratti, Veronique

    AU - Gea, Francisco

    AU - Buti, Maria

    AU - Olveira, Antonio

    AU - Banyai, Tivadar

    AU - Al-Assi, M. Tarek

    AU - Petersen, Joerg

    AU - Thabut, Dominique

    AU - Gadano, Adrian

    AU - Pruitt, Ronald

    AU - Makara, Mihály

    AU - Bourlière, Marc

    AU - Pol, Stanislas

    AU - Beumont-Mauviel, Maria

    AU - Ouwerkerk-Mahadevan, Sivi

    AU - Picchio, Gaston

    AU - Bifano, Marc

    AU - Mcphee, Fiona

    AU - Boparai, Navdeep

    AU - Cheung, Kin

    AU - Hughes, Eric A.

    AU - Noviello, Stephanie

    PY - 2016/2/1

    Y1 - 2016/2/1

    N2 - Background & Aims We evaluated the combination of daclatasvir (pan-genotypic NS5A inhibitor) and simeprevir (NS3/4A protease inhibitor), with or without ribavirin, in hepatitis C virus genotype 1-infected patients. Methods This phase II, open-label study enrolled treatment-naive patients or prior null responders with genotype 1b (n = 147) or 1a (n = 21) infection. Genotype 1b-infected patients were randomized 1:1 to receive daclatasvir 30 mg plus simeprevir 150 mg once daily with or without ribavirin; those who completed the initial 12-week treatment were re-randomized 1:1 to stop treatment or continue treatment through to week 24. Genotype 1a-infected patients received daclatasvir plus simeprevir with ribavirin for 24 weeks. The primary endpoint was the proportion of patients with sustained virologic response at posttreatment week 12 (SVR12). Results For genotype 1b, 84.9% (45/53) and 74.5% (38/51) of treatment-naive patients and 69.6% (16/23) and 95.0% (19/20) of prior null responders to peginterferon and ribavirin achieved SVR12 with daclatasvir plus simeprevir alone and with ribavirin, respectively. Treatment duration did not have a well-defined impact on response. For genotype 1a, daclatasvir plus simeprevir with ribavirin provided a 66.7% (8/12) response rate in treatment-naive patients and was not effective in prior null responders. Data suggest that baseline resistance polymorphisms influenced SVR12 rates. Daclatasvir plus simeprevir was well tolerated with or without ribavirin with low incidences of serious adverse events and adverse events leading to discontinuation. Conclusions Daclatasvir plus simeprevir, with or without ribavirin, was effective with a 12- or 24-week duration in genotype 1b-infected patients and was well tolerated. ClinicalTrials.gov identifier: NCT01628692.

    AB - Background & Aims We evaluated the combination of daclatasvir (pan-genotypic NS5A inhibitor) and simeprevir (NS3/4A protease inhibitor), with or without ribavirin, in hepatitis C virus genotype 1-infected patients. Methods This phase II, open-label study enrolled treatment-naive patients or prior null responders with genotype 1b (n = 147) or 1a (n = 21) infection. Genotype 1b-infected patients were randomized 1:1 to receive daclatasvir 30 mg plus simeprevir 150 mg once daily with or without ribavirin; those who completed the initial 12-week treatment were re-randomized 1:1 to stop treatment or continue treatment through to week 24. Genotype 1a-infected patients received daclatasvir plus simeprevir with ribavirin for 24 weeks. The primary endpoint was the proportion of patients with sustained virologic response at posttreatment week 12 (SVR12). Results For genotype 1b, 84.9% (45/53) and 74.5% (38/51) of treatment-naive patients and 69.6% (16/23) and 95.0% (19/20) of prior null responders to peginterferon and ribavirin achieved SVR12 with daclatasvir plus simeprevir alone and with ribavirin, respectively. Treatment duration did not have a well-defined impact on response. For genotype 1a, daclatasvir plus simeprevir with ribavirin provided a 66.7% (8/12) response rate in treatment-naive patients and was not effective in prior null responders. Data suggest that baseline resistance polymorphisms influenced SVR12 rates. Daclatasvir plus simeprevir was well tolerated with or without ribavirin with low incidences of serious adverse events and adverse events leading to discontinuation. Conclusions Daclatasvir plus simeprevir, with or without ribavirin, was effective with a 12- or 24-week duration in genotype 1b-infected patients and was well tolerated. ClinicalTrials.gov identifier: NCT01628692.

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