Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.
|Number of pages||8|
|Journal||Journal of Gastroenterology and Hepatology (Australia)|
|Publication status||Published - 2017 Dec|
Bibliographical noteFunding Information:
consulted for AbbVie, BMS, Gilead, J&J, Novartis, and Roche, and been on speakers’ bureaus for AbbVie, Roche, BMS, Gilead, and Novartis. M. L. Y. has received grants/funding from Roche, BMS, Gilead, AbbVie, Abbott, and MSD, and received other funding from Bayer, Boehringer, and Novartis. C. Y. P. has served as an advisory committee member for AbbVie, BMS, Gilead, MSD, and F. Hoffmann-La Roche. J. H. has received research grants from BMS and F. Hoffmann-La Roche, and acted as an advisor for AbbVie, BMS, Gilead, and J&J. S. W. P. has received grant and research support from AbbVie, BMS, Gilead, GSK, Merck, Novartis, and Roche. Y. S. L. has served as an advisory board member of Bayer Healthcare, BMS, and Gilead, and received research funding from Bayer Healthcare, BMS, Gilead, and Novartis. S. H. A. has received unrestricted research grants from BMS, Gilead, and Roche, and acted as an advisor and lecturer for BMS, Gilead, Roche, AbbVie, GreenCross, and ABIVAX. V. I. has served as an advisory board member and/or consultant for AbbVie, Vertex, Roche, Novartis, Janssen, R-PHARM, Gilead, and BMS; served on speakers’ bureaus for BMS, Janssen, Roche, Gilead, R-PHARM,
and Novartis; received travel funding from BMS, AbbVie, R-PHARM, and MSD Russia. C. J. C., T. T. C., Y. J. L., T. H. H., and K. T. Y. have nothing to disclose. F. McP., W. H., E. S. S., and M. T. are employees of BMS. P. D. Y. was a BMS employee at the time of the study. Author contribution: M. T., F. McP., W. H., E. S. S., and P. Y. were involved in the study concept and design, data acquisition, analysis and interpretation, and drafting of the manuscript. All other authors were involved in data acquisition and interpretation and critical revision of the manuscript for important intellectual content.
The authors thank the patients and their families, study investigators, and site personnel for their participation. The study was funded, designed, and conducted by the sponsor (BMS) in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analysis. Joseph Ueland, Vincent Vellucci, and Dennis Hernandez are also acknowledged for their efforts obtaining genotypic resistance data on samples from the patients infected with GT-6g. Medical writing assistance was provided by Andrew Street of Articulate Science Ltd, funded by BMS.
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