Daclatasvir and sofosbuvir with ribavirin for 24 weeks in chronic hepatitis C genotype-3-infected patients with cirrhosis: a Phase III study (ALLY-3C).

BACKGROUND: Optimal treatment for patients with hepatitis C virus (HCV) genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks.

METHODS: This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks' daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% confidence interval [CI] lower bound >79.0%).

RESULTS: Seventy-eight patients were treated (54 treatment-naive, 24 treatment-experienced including 8 with prior sofosbuvir exposure). SVR12 was achieved by 87% (68/78; 95% CI 77.7-93.7%) of patients in the primary analysis of central laboratory data. One additional patient achieved SVR12 by local testing resulting in an overall SVR12 rate of 88% (95% CI 79.2-94.6%), and the lower-bound of 95% CI above the historical threshold. SVR12 rates were 93% (50/54) for treatment-naive and 79% (19/24) for treatment-experienced patients. Of the nine non-SVR12 patients, four were lost to follow-up, two relapsed [both sofosbuvir-experienced], two had end-of-treatment virological failure and one discontinued early. There were no unexpected safety signals; only one patient discontinued for an adverse event.

CONCLUSIONS: Daclatasvir+sofosbuvir+ribavirin for 24 weeks was well tolerated and efficacious in HCV genotype-3-infected patients with compensated cirrhosis, with SVR12 outcomes comparable to previously reported outcomes in patients treated with this regimen for 12-16 weeks.