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

Abstract

BACKGROUND:

Optimal treatment for patients with 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 end point 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% CI lower bound >79.0%).

RESULTS:

A total of 78 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 the 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. ClinicalTrials.gov ID NCT02673489.

• Authors: Fred Poordad, Mitchell L Shiffman, Wayne Ghesquiere, Alexander Wong, Gregory D Huhn, Florence Wong, Alnoor Ramji, Stephen D Shafran, Fiona McPhee, Rong Yang, Stephanie Noviello, Misti Linaberry, ALLY-3C study team
• Journal: Antiviral therapy (Antivir Ther) Vol. 24 Issue 1 Pg. 35-44 ( 2019) ISSN: 2040-2058 [Electronic] England
• PMID: 30382942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Pyrrolidines
• Ribavirin
• Valine
• daclatasvir
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Carbamates
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (drug therapy)
• Humans
• Imidazoles (administration & dosage, therapeutic use)
• Liver Cirrhosis (drug therapy)
• Male
• Middle Aged
• Pyrrolidines
• Ribavirin (administration & dosage, therapeutic use)
• Sofosbuvir (administration & dosage, therapeutic use)
• Sustained Virologic Response
• Valine (analogs & derivatives)