title: Efficacy and safety of simeprevir with PegIFN/ribavirin in naïve or experienced patients infected with chronic HCV genotype 4.
abstract: OBJECTIVE
  Simeprevir (SMV) is a once-daily (QD), oral hepatitis C virus (HCV) NS3/4A protease inhibitor approved for treatment of genotype (GT) 1 and GT4 infection. This Phase III, open-label, single-arm study (RESTORE; NCT01567735) evaluated efficacy/safety of SMV with peginterferon-α-2a/ribavirin (PR) in patients with chronic HCV GT4 infection.
  
  
  METHODS
  107 patients were included. Treatment-naïve (n=35) and prior relapse patients (n=22) received SMV 150mg QD+PR (12 weeks), followed by PR alone (12 or 36 weeks, response-guided [HCV RNA <25IU/ml detectable/undetectable at week 4 and <25IU/ml undetectable at week 12]). Prior non-responders (partial, n=10; null, n=40) received SMV/PR (12 weeks), followed by PR for 36 weeks. The primary endpoint was sustained virologic response 12 weeks after end of treatment (SVR12).
  
  
  RESULTS
  Median age: 49.0years; 28.0% Black/African; 7.5% IL28B CC; 28.8% METAVIR F4. Overall, 65.4% (70/107) of patients achieved SVR12 (82.9% [29/35] treatment-naïve; 86.4% [19/22] prior relapsers; 60.0% [6/10] prior partial responders; 40.0% [16/40] prior null responders). In treatment-naïve and prior relapser patients fulfilling response-guided criteria for 24 weeks of treatment (88.6% [31/35] and 90.9% [20/22]), SVR12 rates were high: 93.5% [29/31] and 95.0% [19/20], respectively. Overall on-treatment failure and relapse rates were 23.4% (25/107) and 14.6% (12/82), respectively. Adverse events (AEs) were mainly grade 1/2; serious AEs were infrequent (4.7%) and considered unrelated to SMV.
  
  
  CONCLUSIONS
  Efficacy and safety of SMV 150mg QD for 12 weeks with PR in treatment-naïve or -experienced patients with chronic HCV GT4 infection were in line with previous reports for HCV GT1 infection.
authors.affiliation: CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: Christophe.Moreno@erasme.ulb.ac.be.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hezode
authors.affiliation: Hôpital Beaujon, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: ZNA Campus Stuivenberg, Antwerp, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bourgeois
authors.affiliation: UZ Antwerpen, Antwerp, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
authors.affiliation: Hôpital Paul-Brousse, Centre Hépatobiliaire, Université Paris Sud, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Hôpital de la Croix Rousse, Hepatology Department, Hospices Civils de Lyon and INSERM U1052, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: Hôpital Tenon, AP-HP, Université Pierre et Marie Curie, Paris, France.
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Grange
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Umesh
authors.initials: U
authors.lastname: Shukla
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Sivi
authors.initials: S
authors.lastname: Ouwerkerk-Mahadevan
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Fevery
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jessner
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000208:ethnology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; 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; D055502:Secondary Prevention; D000069616:Simeprevir / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000379:methods
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a
keywords: Chronic; Efficacy; Genotype 4; Hepatitis C virus; Protease inhibitor; Response-guided; Safety; Simeprevir; Sustained virologic response; TMC435 (10/10)