Author information
1 Professor, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI. Electronic address: aslok@med.umich.edu.
2 Professor, Divisions of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD.
3 Senior Medical Director, Medical Affairs, AbbVie Inc, Mettawa, IL.
4 Associate Professor, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC.
5 Professor, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA.
6 Hepatologist, Bon Secours Liver Institute of Richmond, Richmond, VA.
7 Associate Professor, Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN.
8 Medical Director, Center for Hepatitis C, Wellstar Health System, Atlanta, GA.
9 Associate Medical Director, Orlando Immunology Center, Orlando, FL.
10 Professor of Medicine and Director, Hepatology, New York University Langone Health, New York, NY.
11 Assistant Professor, Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL.
12 Assistant Director, Hepatology Research, University of Florida, Gainesville, FL.
13 Director, Biometrics and Data Quality HCV-TARGET Data Coordinating Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
14 Biostatistician, HCV-TARGET Data Coordinating Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
15 Professor, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
16 Associate Professor, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL.
17 Manager, Statistics, AbbVie Inc, North Chicago, IL.
18 Senior Director Statistics, TA Head Virology and General Medicine, Abbvie Inc., North Chicago, IL.
19 Professor of Medicine, Department of Medicine, University of Florida, Gainesville, FL.
Abstract
BACKGROUND/AIMS:
Treatment options are limited for patients with hepatitis C (HCV) infection with treatment failure after sofosbuvir plus an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients. We performed a randomized trial of the safety and efficacy of 12 and 16 weeks of G/P, with or without ribavirin, in patients with HCV genotype 1 infection with treatment failure after sofosbuvir and an NS5A inhibitor.
METHODS:
We performed a phase 3b, open label study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks (n=78, group A) or 16 weeks (n=49, group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks (n=21, group C) or G/P for 16 weeks (n=29, group D). The primary endpoint was a sustained virologic response 12 weeks after treatment (SVR12). Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions (RASs) in NS3 and NS5A.
RESULTS:
Of the 177 patients in the 4 groups, 81% were men, 79% had HCV genotype 1a infection, and 44% were black. Proportions of patients with an SVR12 in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 patients with HCV genotype 1a infection (7.3%), 6 in group A (7.9%), 3 in group B (6.1%), 3 in group C (14.3%), and 1 in group D (3.4%). Most patients had baseline RASs in NS5A. Treatment-emergent RASs in NS3 and NS5A were observed in 9 and 10 patients with treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events but did not increase efficacy.
CONCLUSIONS:
In a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produced an SVR12 in more than 90% of patients, including those with compensated cirrhosis. ClinicalTrials.gov no: NCT03092375.