title: An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1).
abstract: BACKGROUND
  Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.
  
  
  METHODS
  In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA <25 IU/mL (detectable/undetectable) at Week 2, and undetectable HCV-RNA at Weeks 4 and 8, stopped all treatment at Week 12. All other patients continued PR for a further 12 weeks. Baseline factors significantly associated with SVR12 were identified through logistic regression.
  
  
  RESULTS
  Of 163 patients who participated in the study, 123 (75%) qualified for 12-week treatment; of these, 81 (66%) achieved SVR12. Baseline factors positively associated with SVR12 rates in patients receiving the 12-week regimen were: IL28B CC genotype: (94% SVR12); HCV RNA ≤800,000 IU/mL (82%); F0-F1 fibrosis (74%). Among all 163 patients, 94% experienced ≥1 adverse event (AE), 4% a serious AE, and 2.5% discontinued due to an AE. Reduced impairment in patient-reported outcomes was observed in the 12-week vs >12-week regimen.
  
  
  CONCLUSIONS
  Overall SVR12 rate (66%) was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01846832.
authors.affiliation: Service d'Hépatologie, Beaujon Hospital, INSERM UMR 1149, Université Paris Diderot, Paris, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Wilhelminenspital, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Gschwantler
authors.affiliation: Queen Mary Hospital, University of London, Barts Health, London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxí
authors.affiliation: Institute for Interdisciplinary Medicine, Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.affiliation: Janssen Research & Development, Titusville, New Jersey, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Global Services, High Wycombe, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Scott
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Gino
authors.initials: G
authors.lastname: Van Dooren
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.affiliation: Janssen-Cilag, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlag
authors.affiliation: Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069616:Simeprevir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069616:Simeprevir