Simeprevir with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trial

Background 82 Aims: In a Japanese Phase II study, the hepatitis C virus NS3/4A protease inhibitor simeprevir demonstrated potent antiviral activity and significantly improved sustained virologic response rates when added to peginterferon alpha-2a/ribavirin in treatment-naive patients infected with hepatitis C virus genotype 1. Methods: CONCERTO-1 was a Phase III, randomized, double-blind, placebo-controlled trial. Treatment-naive adults (<= 70 years) with chronic hepatitis C virus genotype 1 infection (hepatitis C virus RNA >= 5 log(10) IU/ml) were randomized (2:1) to simeprevir 100 mg once-daily with peginterferon alpha-2a/ribavirin for 12 weeks then response-guided therapy with peginterferon alpha-2a/ribavirin for 12 or 36 weeks, or to placebo with peginterferon alpha-2a/ribavirin for 12 weeks then peginterferon alpha-2a/ribavirin for 36 weeks. Results: Overall, 183 patients were treated. Sustained virologic response 12 weeks after treatment end (primary efficacy endpoint) was achieved in 88.6% of simeprevir- and 61.7% of placebo-treated patients (p <0.0001 for stratum-adjusted between-group difference). Overall, 91.9% of simeprevir-treated patients met response-guided therapy criteria and completed treatment at week 24; sustained virologic response rate at 12 weeks in these patients was 92.0%. One simeprevir- (0.8%) and two placebo-treated patients (3.3%) experienced viral breakthrough; respective viral relapse rates were 7.6% and 30.6%. Overall adverse event profile in simeprevir-treated patients was comparable to that in patients who received peginterferon alpha-2a/ribavirin alone. Conclusions: Simeprevir once daily with peginterferon alpha-2a/ ribavirin significantly improved sustained virologic response rate 12 weeks after treatment end in treatment-naive patients with chronic hepatitis C virus genotype 1 infection, with a shorter 24-week treatment duration in most patients. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.