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Abstract Details
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
Author information
1Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA. Electronic address: lawitz@txliver.com.
2Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3Texas Clinical Research Institute, Arlington, TX, USA.
4Fundación de Investigación, San Juan, PR, USA.
5Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.
6Borland-Groover Clinic, Jacksonville, FL, USA.
7Orlando Immunology Center, Orlando, FL, USA.
8Atlanta Medical Center, Atlanta, GA, USA.
9University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
10Atlanta Gastroenterology Association, Atlanta, GA, USA.
11Yale Liver Center and Yale University School of Medicine, New Haven, CT, USA.
12Scripps Clinic, La Jolla, CA, USA.
13Harborview Medical Center, Seattle, WA, USA.
14Janssen Research & Development, Beerse, Belgium.
15Novellas Healthcare, Zellik, Belgium.
16Gilead Sciences Inc, Foster City, CA, USA.
17Janssen Research & Development, Titusville, NJ, USA.
18Weill Cornell Medical College, New York, NY, USA.
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 2:2:1:1 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.