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J Hepatol. 2014 Aug;61(2):219-27. doi: 10.1016/j.jhep.2014.04.004. Epub 2014 Apr 12.

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

Author information

1
Kansai Rosai Hospital, Hyogo, Japan.
2
Musashino Red-Cross Hospital, Tokyo, Japan.
3
Toranomon Hospital, Tokyo, Japan.
4
Saiseikai Suita Hospital, Osaka, Japan.
5
Kagoshima University Medical and Dental Hospital, Kagoshima, Japan.
6
National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.
7
Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan.
8
Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan. Electronic address: SGOTO2@its.jnj.com.

Abstract

BACKGROUND & 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 α-2a/ribavirin in treatment-naïve patients infected with hepatitis C virus genotype 1.

METHODS:

CONCERTO-1 was a Phase III, randomized, double-blind, placebo-controlled trial. Treatment-naïve adults (⩽ 70 years) with chronic hepatitis C virus genotype 1 infection (hepatitis C virus RNA ⩾ 5 log10 IU/ml) were randomized (2:1) to simeprevir 100mg once-daily with peginterferon α-2a/ribavirin for 12 weeks then response-guided therapy with peginterferon α-2a/ribavirin for 12 or 36 weeks, or to placebo with peginterferon α-2a/ribavirin for 12 weeks then peginterferon α-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 α-2a/ribavirin alone.

CONCLUSIONS:

Simeprevir once daily with peginterferon α-2a/ribavirin significantly improved sustained virologic response rate 12 weeks after treatment end in treatment-naïve patients with chronic hepatitis C virus genotype 1 infection, with a shorter 24-week treatment duration in most patients.

KEYWORDS:

Genotype 1; Hepatitis C virus; Once-daily; Peginterferon; Protease inhibitor; Ribavirin; Simeprevir; TMC435; Treatment-naïve

PMID:
24727123
DOI:
10.1016/j.jhep.2014.04.004
[Indexed for MEDLINE]
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