title: Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin.
abstract: Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.
authors.affiliation: Department of Hepatology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Department of Medicine III, University Hospital Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Service d'Hépatologie, AP-HP, University Paris-Diderot and INSERM U773, CRB3, Hôpital Beaujon, Clichy, France.
authors.forename: T
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Department of Hepatology, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mantry
authors.affiliation: Department of Hepatology, University Clinic for Visceral Surgery and Medicine and University of Bern, Bern, Switzerland.
authors.forename: J-F
authors.initials: JF
authors.lastname: Dufour
authors.affiliation: Département d'Hépato-gastroentérologie, Hôpital Saint Joseph, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: Department of Gastroenterology and Hepatology, St George's Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Forton
authors.affiliation: Hepatology Department, First Moscow State Medical University, Moscow, Russia.
authors.forename: M
authors.initials: M
authors.lastname: Maevskaya
authors.affiliation: Central Texas Clinical Research, Austin, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wright
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: E M
authors.initials: EM
authors.lastname: Yoshida
authors.affiliation: Liver Unit, Hospital Universitario La Paz/Carlos III CIBERehd, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: García-Samaniego
authors.affiliation: Department of Radiology, Hospital Infante D. Pedro, Aveiro, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Oliveira
authors.affiliation: Wellcome Trust Clinical Research Facility, Southampton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.affiliation: Boehringer Ingelheim Ltd., Bracknell, UK.
authors.forename: N
authors.initials: N
authors.lastname: Warner
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: N
authors.initials: N
authors.lastname: Sha
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: A-M
authors.initials: AM
authors.lastname: Quinson
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: J O
authors.initials: JO
authors.lastname: Stern
mesh_terms: D000328:Adult; D000368:Aged; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D010919:Placebos / Q000008:administration & dosage; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D012254:Ribavirin / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000379:methods*; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D010919:Placebos; D011804:Quinolines; D013844:Thiazoles; D012254:Ribavirin; C552340:faldaprevir; D011392:Proline; D007930:Leucine
keywords: NS3/4A protease inhibitor; faldaprevir; hepatitis C virus; sustained virological response; treatment-experienced