Author information
1
The Texas Liver Institute, University of Texas Health, San Antonio, TX, USA.
2
Bon Secours Liver Institute of Richmond, Bon Secours Health System of Virginia, Richmond, VA, USA.
3
PerCuro Clinical Research Ltd, Victoria, BC, Canada.
4
Regina General Hospital, University of Saskatchewan, Regina, SK, Canada.
5
Ruth M. Rothstein CORE Center, Chicago, IL, USA.
6
Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
7
Gastroenterology Division, St Paul's Hospital, Vancouver, BC, Canada.
8
University of Alberta, Edmonton, AB, Canada.
9
Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
10
Bristol-Myers Squibb, Princeton, NJ, USA.
Abstract
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.