title: STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection.
abstract: OBJECTIVE
  The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection.
  
  
  METHODS
  Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12).
  
  
  RESULTS
  SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components.
  
  
  CONCLUSIONS
  Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. Electronic address: peter.ferenci@meduniwien.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Department of Hepatology, Hôpital Beaujon, APHP, University Paris-Diderot and INSERM CRB3, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Department of Hepatology, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Department of Internal Medicine, JW Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Department of Internal Medicine, JW Goethe University Hospital, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Department of Hepato-gastroenterology, Institut Arnault Tzanck, St Laurent du Var, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Ouzan
authors.affiliation: Hepatology Department, First Moscow State Medical University, Moscow, Russia.
authors.forename: Marina
authors.initials: M
authors.lastname: Maevskaya
authors.affiliation: Gastroenterology Service, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Calinas
authors.affiliation: Department of Internal Medicine - Infectious Diseases, Hospital Meixoeiro, Vigo, Spain.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Morano
authors.affiliation: Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.affiliation: Department of Hepatology, University Clinic for Visceral Surgery and Medicine, Bern, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dufour
authors.affiliation: Département d'Hépato-gastroentérologie, Hôpital Saint Joseph, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK.
authors.forename: Kosh
authors.initials: K
authors.lastname: Agarwal
authors.affiliation: Department of Gastroenterology and Hepatology, St George's Hospital, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Forton
authors.affiliation: 1st Department of Medicine, University Hospital Mainz, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.affiliation: Gastroenterological Practice, Schwerpunktpraxis Hepatologie, Dortmund, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Zehnter
authors.affiliation: Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: Department of Gastroenterology, Yamanishi Central and Kita Hospitals, Yamanishi, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, GmbH & Co. KG, Biberach, Germany.
authors.forename: Yakov
authors.initials: Y
authors.lastname: Datsenko
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Scherer
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Quinson
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
mesh_terms: D000328:Adult; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011804:Quinolines; D012367:RNA, Viral; D011994:Recombinant Proteins; D013844:Thiazoles; D011092:Polyethylene Glycols; D012254:Ribavirin; C552340:faldaprevir; D011392:Proline; D007930:Leucine; C100416:peginterferon alfa-2a
keywords: Clinical trial; DAA; Early treatment success; NS3/4A protease inhibitor; Phase 3; SVR12