Anna S Lok1, Mark S Sulkowski2, Jens J Kort3, Ira Willner4, K Rajender Reddy5, Mitchell L Shiffman6, Mohamed A Hassan7, Brian L Pearlman8, Federico Hinestrosa9, Ira M Jacobson10, Giuseppe Morelli11, Joy A Peter12, Monika Vainorius13, Larry C Michael13, Michael W Fried14, Gary P Wang15, Wenjing Lu16, Lois Larsen16, David R Nelson17. 1. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan. Electronic address: aslok@med.umich.edu. 2. Divisions of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. AbbVie Inc, Mettawa, Illinois. 4. Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina. 5. Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Bon Secours Liver Institute of Richmond, Richmond, Virginia. 7. Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota. 8. Center for Hepatitis C, Wellstar Health System, Atlanta, Georgia. 9. Orlando Immunology Center, Orlando, Florida. 10. Department of Hepatology, New York University Langone Health, New York, New York. 11. Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida. 12. Hepatology Research, University of Florida, Gainesville, Florida. 13. HCV-TARGET Data Coordinating Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 14. Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 15. Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, Florida. 16. AbbVie Inc, North Chicago, Illinois. 17. Department of Medicine, University of Florida, Gainesville, Florida.
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 end point was a sustained virologic response 12 weeks after treatment. Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions 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 sustained virologic response 12 weeks after treatment in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C (6.1%), and 1 (3.4%) in group D. Most patients had baseline resistance-associated substitutions in NS5A. Treatment-emergent resistance-associated substitutions 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 sustained virologic response 12 weeks after treatment in >90% of patients, including those with compensated cirrhosis. ClinicalTrials.gov, Number: NCT03092375.
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 end point was a sustained virologic response 12 weeks after treatment. Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions 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 sustained virologic response 12 weeks after treatment in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C (6.1%), and 1 (3.4%) in group D. Most patients had baseline resistance-associated substitutions in NS5A. Treatment-emergent resistance-associated substitutions 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 sustained virologic response 12 weeks after treatment in >90% of patients, including those with compensated cirrhosis. ClinicalTrials.gov, Number: NCT03092375.
Authors: Haesuk Park; Wei-Hsuan Lo-Ciganic; James Huang; Yonghui Wu; Linda Henry; Joy Peter; Mark Sulkowski; David R Nelson Journal: Hepatology Date: 2022-02-03 Impact factor: 17.298