Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial. Academic Article uri icon

Overview

abstract

  • BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.

authors

  • Brown, Robert S.
  • Buti, Maria
  • Rodrigues, Lino
  • Chulanov, Vladimir
  • Chuang, Wan-Long
  • Aguilar, Humberto
  • Horváth, Gábor
  • Zuckerman, Elimelech
  • Carrion, Barbara Rosado
  • Rodriguez-Perez, Federico
  • Urbánek, Petr
  • Abergel, Armand
  • Cohen, Eric
  • Lovell, Sandra S
  • Schnell, Gretja
  • Lin, Chih-Wei
  • Zha, Jiuhong
  • Wang, Stanley
  • Trinh, Roger
  • Mensa, Federico J
  • Burroughs, Margaret
  • Felizarta, Franco

publication date

  • November 2, 2019

Research

keywords

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Cyclopropanes
  • Genotype
  • Hepacivirus
  • Hepatitis C, Chronic
  • Lactams, Macrocyclic
  • Leucine
  • Liver Cirrhosis
  • Proline
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides

Identity

Scopus Document Identifier

  • 85075376406

Digital Object Identifier (DOI)

  • 10.1016/j.jhep.2019.10.020

PubMed ID

  • 31682879

Additional Document Info

volume

  • 72

issue

  • 3