Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial

Abstract

Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate the safety and efficacy of grazoprevir at doses of 25-100 mg/day in combination with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection received once-daily grazoprevir 25 mg, 50 mg or 100 mg plus PEG-IFN/RBV for 12 weeks. Patients with quantifiable HCV RNA (≥25 IU/mL) at week 4 received an additional 12 weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic response (HCV RNA <25 IU/mL 12 weeks after completing therapy [SVR12]). Eighty-seven patients were randomly assigned and received ≥1 dose of therapy. Median time to undetectable HCV RNA was 16 days in the 100-mg arm and 22 days in the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or unquantifiable at week 4 and received 12 weeks of therapy. SVR12 was achieved by 13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- and 100-mg arms, respectively (per-protocol analysis). Three patients discontinued as a result of nonserious adverse events (AEs) and three patients experienced serious AEs. Transaminase elevations occurred in two patients (one each in the 25- and 100-mg arms).

Conclusion: These data support further study of the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100 mg in combination with elbasvir are currently ongoing (NCT01710501; protocol P038).

Keywords: adverse event; clinical trial; direct-acting antiviral drugs; resistance; sustained virologic response.