Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial
| Autor: | Federico Rodriguez-Perez, Barbara Rosado Carrion, Humberto Aguilar, Vladimir Chulanov, Sandra S. Lovell, Lino Rodrigues, Eric Cohen, Robert S. Brown, Maria Buti, Chih-Wei Lin, Federico J. Mensa, Margaret Burroughs, Roger Trinh, Petr Urbánek, Stanley Wang, Wan-Long Chuang, Gabor Horvath, Jiuhong Zha, Gretja Schnell, Franco Felizarta, Armand Abergel, E. Zuckerman |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cyclopropanes Liver Cirrhosis Male medicine.medical_specialty Cirrhosis Aminoisobutyric Acids Pyrrolidines Genotype Proline Sustained Virologic Response Nausea Lactams Macrocyclic Population Hepacivirus Viral Nonstructural Proteins Antiviral Agents 03 medical and health sciences 0302 clinical medicine Leucine Internal medicine Quinoxalines medicine Humans education Adverse effect Aged education.field_of_study Sulfonamides Polymorphism Genetic Hepatology business.industry Glecaprevir Hepatitis C Chronic Middle Aged medicine.disease Pibrentasvir Discontinuation Regimen Drug Combinations 030104 developmental biology RNA Viral 030211 gastroenterology & hepatology Benzimidazoles Female medicine.symptom business |
| Zdroj: | Journal of hepatology. 72(3) |
| ISSN: | 1600-0641 |
| Popis: | 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-naive patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naive 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-naive 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. |
| Databáze: | OpenAIRE |
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