Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: The COSMOS randomised study

Eric Lawitz, Mark Sulkowski, Reem Ghalib, Maribel Rodriguez-Torres, Zobair M. Younossi, Ana Corregidor, Edwin Dejesus, Brian Pearlman, Mordechai Rabinovitz, Norman Gitlin, Joseph K. Lim, Paul J. Pockros, John D. Scott, Bart Fevery, Tom Lambrecht, Sivi Ouwerkerk-Mahadevan, Katleen Callewaert, William T. Symonds, Gaston Picchio, Karen L. LindsayMaria Beumont, Ira M. Jacobson

Research output: Contribution to journalArticle

Abstract

Background Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.

Methods We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790.

Findings 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12.

Interpretation Combined simeprevir and sofosbuvir was efficacious and well tolerated. Funding Janssen.

Original languageEnglish (US)
Pages (from-to)1756-1765
Number of pages10
JournalThe Lancet
Volume384
Issue number9956
DOIs
StatePublished - Nov 15 2014

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Ribavirin
Hepacivirus
Interferons
Genotype
Infection
Therapeutics
Simeprevir
Sofosbuvir
Chronic Hepatitis C
Virus Diseases
Amylases
Nausea
Fatigue
Headache
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients : The COSMOS randomised study. / Lawitz, Eric; Sulkowski, Mark; Ghalib, Reem; Rodriguez-Torres, Maribel; Younossi, Zobair M.; Corregidor, Ana; Dejesus, Edwin; Pearlman, Brian; Rabinovitz, Mordechai; Gitlin, Norman; Lim, Joseph K.; Pockros, Paul J.; Scott, John D.; Fevery, Bart; Lambrecht, Tom; Ouwerkerk-Mahadevan, Sivi; Callewaert, Katleen; Symonds, William T.; Picchio, Gaston; Lindsay, Karen L.; Beumont, Maria; Jacobson, Ira M.

In: The Lancet, Vol. 384, No. 9956, 15.11.2014, p. 1756-1765.

Research output: Contribution to journalArticle

Lawitz, E, Sulkowski, M, Ghalib, R, Rodriguez-Torres, M, Younossi, ZM, Corregidor, A, Dejesus, E, Pearlman, B, Rabinovitz, M, Gitlin, N, Lim, JK, Pockros, PJ, Scott, JD, Fevery, B, Lambrecht, T, Ouwerkerk-Mahadevan, S, Callewaert, K, Symonds, WT, Picchio, G, Lindsay, KL, Beumont, M & Jacobson, IM 2014, 'Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: The COSMOS randomised study', The Lancet, vol. 384, no. 9956, pp. 1756-1765. https://doi.org/10.1016/S0140-6736(14)61036-9
Lawitz, Eric ; Sulkowski, Mark ; Ghalib, Reem ; Rodriguez-Torres, Maribel ; Younossi, Zobair M. ; Corregidor, Ana ; Dejesus, Edwin ; Pearlman, Brian ; Rabinovitz, Mordechai ; Gitlin, Norman ; Lim, Joseph K. ; Pockros, Paul J. ; Scott, John D. ; Fevery, Bart ; Lambrecht, Tom ; Ouwerkerk-Mahadevan, Sivi ; Callewaert, Katleen ; Symonds, William T. ; Picchio, Gaston ; Lindsay, Karen L. ; Beumont, Maria ; Jacobson, Ira M. / Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients : The COSMOS randomised study. In: The Lancet. 2014 ; Vol. 384, No. 9956. pp. 1756-1765.
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abstract = "Background Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.Methods We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790.Findings 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92{\%}) patients (n=72 [90{\%}, 95{\%} CI 81-96] in cohort 1 and n=82 [94{\%}, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31{\%}]), headache (n=33 [20{\%}]), and nausea (n=26 [16{\%}]). Grade 4 adverse events were seen in one (2{\%}) of 54 patients in each of groups 1 and 3 and in three (10{\%}) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5{\%} of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2{\%}) patients, all in groups 1 and 2. Four (2{\%}) patients discontinued all study treatment because of adverse events, three before week 12.Interpretation Combined simeprevir and sofosbuvir was efficacious and well tolerated. Funding Janssen.",
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T1 - Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients

T2 - The COSMOS randomised study

AU - Lawitz, Eric

AU - Sulkowski, Mark

AU - Ghalib, Reem

AU - Rodriguez-Torres, Maribel

AU - Younossi, Zobair M.

AU - Corregidor, Ana

AU - Dejesus, Edwin

AU - Pearlman, Brian

AU - Rabinovitz, Mordechai

AU - Gitlin, Norman

AU - Lim, Joseph K.

AU - Pockros, Paul J.

AU - Scott, John D.

AU - Fevery, Bart

AU - Lambrecht, Tom

AU - Ouwerkerk-Mahadevan, Sivi

AU - Callewaert, Katleen

AU - Symonds, William T.

AU - Picchio, Gaston

AU - Lindsay, Karen L.

AU - Beumont, Maria

AU - Jacobson, Ira M.

PY - 2014/11/15

Y1 - 2014/11/15

N2 - Background Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.Methods We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790.Findings 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12.Interpretation Combined simeprevir and sofosbuvir was efficacious and well tolerated. Funding Janssen.

AB - Background Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.Methods We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790.Findings 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12.Interpretation Combined simeprevir and sofosbuvir was efficacious and well tolerated. Funding Janssen.

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