Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial

Gastroenterology. 2016 Nov;151(5):902-909. doi: 10.1053/j.gastro.2016.07.038. Epub 2016 Jul 30.

Abstract

Background & aims: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients.

Methods: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12).

Results: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events.

Conclusions: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.

Keywords: Clinical Trial; DAA; Direct-Acting Antiviral; Non-Genotype 1 HCV.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Carbamates / therapeutic use*
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Humans
  • Macrocyclic Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Serine Proteases
  • Sofosbuvir / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Viral Nonstructural Proteins
  • Young Adult

Substances

  • Antiviral Agents
  • Carbamates
  • Drug Combinations
  • Heterocyclic Compounds, 4 or More Rings
  • Macrocyclic Compounds
  • Sulfonamides
  • Viral Nonstructural Proteins
  • voxilaprevir
  • NS3-4A serine protease, Hepatitis C virus
  • Serine Proteases
  • velpatasvir
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02378961