1. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial.
- Author
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Brown RS Jr, Buti M, Rodrigues L, Chulanov V, Chuang WL, Aguilar H, Horváth G, Zuckerman E, Carrion BR, Rodriguez-Perez F, Urbánek P, Abergel A, Cohen E, Lovell SS, Schnell G, Lin CW, Zha J, Wang S, Trinh R, Mensa FJ, Burroughs M, and Felizarta F
- Subjects
- Aged, Aminoisobutyric Acids adverse effects, Antiviral Agents adverse effects, Benzimidazoles adverse effects, Cyclopropanes adverse effects, Drug Combinations, Female, Hepacivirus enzymology, Hepatitis C, Chronic blood, Hepatitis C, Chronic virology, Humans, Lactams, Macrocyclic adverse effects, Leucine administration & dosage, Leucine adverse effects, Male, Middle Aged, Polymorphism, Genetic, Proline administration & dosage, Proline adverse effects, Pyrrolidines adverse effects, Quinoxalines adverse effects, RNA, Viral blood, RNA, Viral genetics, Sulfonamides adverse effects, Sustained Virologic Response, Viral Nonstructural Proteins genetics, Aminoisobutyric Acids administration & dosage, Antiviral Agents administration & dosage, Benzimidazoles administration & dosage, Cyclopropanes administration & dosage, Genotype, Hepacivirus genetics, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Lactams, Macrocyclic administration & dosage, Leucine analogs & derivatives, Liver Cirrhosis complications, Liver Cirrhosis drug therapy, Proline analogs & derivatives, Pyrrolidines administration & dosage, Quinoxalines administration & dosage, Sulfonamides administration & dosage
- 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., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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