title: Interferon-free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study.
abstract: OBJECTIVE
  Setrobuvir is a direct-acting antiviral (DAA) non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study examined interferon-free combinations containing setrobuvir, a ritonavir-boosted protease inhibitor (danoprevir/r) and ribavirin, with/without the nucleoside inhibitor mericitabine in HCV genotype (G)1 patients.
  
  
  METHODS
  Non-cirrhotic treatment-naïve patients (N = 110) were randomized to five groups. Three groups received a 14-day mericitabine/ribavirin lead-in followed by treatment with 3 DAAs (setrobuvir, danoprevir/r, mericitabine) plus ribavirin for 12 weeks (Group A: G1a; D: G1b) or 24 weeks (B: G1a), and two groups received 2 DAAs (setrobuvir, danoprevir/r) plus ribavirin for 12 weeks (E: G1b) or 24 weeks (C: G1a). Efficacy was defined as sustained virological response (HCV RNA <25 IU/ml after 12 weeks' follow-up, SVR12).
  
  
  RESULTS
  Two groups met predefined futility criteria for breakthrough (C) or relapse (A) and were discontinued. SVR12 rates were 42.9% (3/7) and 74.1% (20/27) in G1a patients in Groups A and B, respectively, and 95.7% (22/23) and 68.2% (15/22) in G1b patients in Groups D and E respectively. All G1a patients assigned to 24 weeks of treatment who experienced a decrease in HCV RNA of ≥2.3 log10 IU by the end of the lead-in period (n = 28) achieved SVR12. Overall, treatment was well tolerated and most adverse events were mild to moderate. No major safety signals were identified.
  
  
  CONCLUSIONS
  An interferon-free setrobuvir-based regimen (3 DAAs plus ribavirin) is safe and effective in treatment-naïve G1 patients.
authors.affiliation: University of Chicago Medicine, Chicago, IL, USA.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Jensen
authors.affiliation: Roche Innovation Center, New York, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Brunda
authors.affiliation: Roche Products Ltd, Welwyn, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.affiliation: Auckland Clinical Studies, Grafton, New Zealand.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.affiliation: Storr Liver Unit, Westmead Hospital and University of Sydney, Westmead, NSW, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Katerina
authors.initials: K
authors.lastname: Glavini
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Hammond
authors.affiliation: Genentech, South San Francisco, CA, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Pogam
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Isabel
authors.initials: I
authors.lastname: Nájera
authors.affiliation: Roche Innovation Center, New York, NY, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Passe
authors.affiliation: Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Piekarska
authors.affiliation: Roche Innovation Center, New York, NY, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rodriguez
authors.affiliation: Medizinische Klinik I, Johann-Wolfgang-Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Roche Innovation Center, New York, NY, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Chu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D001581:Benzothiadiazines / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D054833:Isoindoles; D007769:Lactams / Q000627:therapeutic use; D047029:Lactams, Macrocyclic; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D010641:Phenotype; D011392:Proline / Q000031:analogs & derivatives; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012074:Remission Induction; D012254:Ribavirin / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
chemical_list: C552098:2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine; D000998:Antiviral Agents; D001581:Benzothiadiazines; D003521:Cyclopropanes; D054833:Isoindoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D015363:Quinolones; D012367:RNA, Viral; D013449:Sulfonamides; D003841:Deoxycytidine; D012254:Ribavirin; D007372:Interferons; C553752:danoprevir; D011392:Proline; C000592794:setrobuvir
keywords: chronic hepatitis C; danoprevir; interferon-free; mericitabine; setrobuvir