Purpose / DescriptionIn this phase 3 placebo-controlled trial, investigators enrolled patients with chronic hepatitis C genotype 1-6 who had previously received treatment that included an NS5A inhibitor. Genotype 1 patients were randomized in a 2:1 ratio to either the active arm, a fixed-dose combination of sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks, or placebo arm (that received sofosbuvir-velpatasvir-voxilaprevir after follow-up). Patients with genotype 2-6 were all assigned to the active arm. Most patients were either ledipasvir- or daclatasvir-experienced (51% and 27% respectively) and compensated cirrhosis was present in 46% of patients in the active arm. The overall sustained virologic response (SVR) 12 rate was 96% by intent-to-treat analysis, with 6 viral relapses among those who failed sofosbuvir-velpatasvir-voxilaprevir. A SVR 12 occurred in 99% of those who were not cirrhotic and 93% of cirrhotic patients. The SVR rates were not associated with the presence of NS5A or other resistance-associated substitutions. Note: this study was published in tandem with the POLARIS-4 study.