Interferon-free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study

Liver Int. 2016 Apr;36(4):505-14. doi: 10.1111/liv.12997. Epub 2015 Dec 12.

Abstract

Background & aims: 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.

Trial registration: ClinicalTrials.gov NCT01628094.

Keywords: chronic hepatitis C; danoprevir; interferon-free; mericitabine; setrobuvir.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Australia
  • Benzothiadiazines / adverse effects
  • Benzothiadiazines / therapeutic use*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Drug Therapy, Combination
  • Europe
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons / adverse effects
  • Interferons / therapeutic use*
  • Lactams / therapeutic use
  • Male
  • Middle Aged
  • New Zealand
  • Phenotype
  • Quinolones / adverse effects
  • Quinolones / therapeutic use*
  • RNA, Viral / blood
  • Remission Induction
  • Ribavirin / therapeutic use
  • Sulfonamides / therapeutic use
  • Time Factors
  • Treatment Outcome
  • United States
  • Viral Load

Substances

  • 2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine
  • Antiviral Agents
  • Benzothiadiazines
  • Lactams
  • Quinolones
  • RNA, Viral
  • Sulfonamides
  • Deoxycytidine
  • Ribavirin
  • Interferons
  • danoprevir
  • setrobuvir

Associated data

  • ClinicalTrials.gov/NCT01628094
  • GENBANK/NCT01628094