title: Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO).
abstract: Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis.
  
  
  
  To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis.
  
  
  
  Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed.
  
  
  
  Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients.
  
  
  
  Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807].
authors.affiliation: Hospital Vall d'Hebron and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Buti
authors.affiliation: University Hospital Puerta de Hierro Majadahonda, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Lens
authors.affiliation: Quirón Valencia Hospital, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Diago
authors.affiliation: Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ortega
authors.affiliation: Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Crespo
authors.affiliation: Hospital Universitari Germans Trias i Pujol (CIBERehd), Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Planas
authors.affiliation: Valme University Hospital University of Seville, Sevilla, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Romero-Gómez
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: F G
authors.initials: FG
authors.lastname: Rodríguez
authors.affiliation: Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Pascasio
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Fevery
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kurland
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Corbett
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kalmeijer
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Jessner
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000821:virology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D000072230:Sustained Virologic Response; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir