1University of Chicago Medicine, Chicago, IL, USA.
2Roche Innovation Center, New York, NY, USA.
3Roche Products Ltd, Welwyn, UK.
4Auckland Clinical Studies, Grafton, New Zealand.
5Storr Liver Unit, Westmead Hospital and University of Sydney, Westmead, NSW, Australia.
6Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
7Genentech, South San Francisco, CA, USA.
8Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland.
9Medizinische Klinik I, Johann-Wolfgang-Goethe University Hospital, Frankfurt, Germany.
BACKGROUND AND 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.
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).
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.
An interferon-free setrobuvir-based regimen (3 DAAs plus ribavirin) is safe and effective in treatment-naïve G1 patients.