title: Simeprevir with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trial.
abstract: OBJECTIVE
  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.
authors.affiliation: Kansai Rosai Hospital, Hyogo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Musashino Red-Cross Hospital, Tokyo, Japan.
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.affiliation: Toranomon Hospital, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: Saiseikai Suita Hospital, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.affiliation: Kagoshima University Medical and Dental Hospital, Kagoshima, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
authors.affiliation: National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.affiliation: Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Kato
authors.affiliation: Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Rito
authors.initials: R
authors.lastname: Ki
authors.affiliation: Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Komada
authors.affiliation: Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Seto
authors.affiliation: Research & Development, Janssen Pharmaceutical K.K., Tokyo, Japan. Electronic address: SGOTO2@its.jnj.com.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069616:Simeprevir; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000069616:Simeprevir; D013449:Sulfonamides; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Genotype 1; Hepatitis C virus; Once-daily; Peginterferon; Protease inhibitor; Ribavirin; Simeprevir; TMC435; Treatment-naïve