The Texas Liver Institute, University of Texas Health, San Antonio, TX, USA.
Bon Secours Liver Institute of Richmond, Bon Secours Health System of Virginia, Richmond, VA, USA.
PerCuro Clinical Research Ltd, Victoria, BC, Canada.
Regina General Hospital, University of Saskatchewan, Regina, SK, Canada.
Ruth M. Rothstein CORE Center, Chicago, IL, USA.
Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
Gastroenterology Division, St Paul's Hospital, Vancouver, BC, Canada.
University of Alberta, Edmonton, AB, Canada.
Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
Bristol-Myers Squibb, Princeton, NJ, USA.
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.
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%).
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.
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.