Background The efficacy, safety, and pharmacokinetics of the combination of three direct-acting antiviral (DAA) agents (adafosbuvir [also known as AL-335], odalasvir, and simeprevir) were investigated in DAA treatment-naïve Japanese patients with genotype (GT)1 or GT2 chronic hepatitis C virus (HCV) infection, with or without compensated cirrhosis. Methods In this Phase IIa, open-label, multicenter study-OMEGA-3 (NCT02993250)-patients received JNJ-4178 (adafosbuvir 800 mg once daily [QD], odalasvir 25 mg QD, and simeprevir 75 mg QD) for 8 (non-cirrhotic patients; Cohort 1) or 12 (cirrhotic patients; Cohort 2) weeks. Patients were followed-up to 24 weeks following the end of treatment (EOT). The primary endpoint was safety, including adverse events (AEs). Results Overall, 33 patients were enrolled into Cohort 1 (N = 22) or 2 (N = 11) and received combined treatment with JNJ-4178. During the treatment and follow-up phases, a higher percentage of patients in Cohort 2 (81.8%)