Potential conflict of interest: Paul Pockros–research support from Genentech/Roche, Vertex, Gilead, Bristol-Myers Squibb, Novartis, Abbott, Intercept, Boehringer Ingelheim, Janssen, Merck and Roche Molecular Diagnostics; consulting and advisory boards for Genentech/Roche, Vertex, Gilead, Bristol-Myers Squibb, Merck, Kadmon, Janssen and Roche Molecular Diagnostics; speaking honoraria from Genentech/Roche, Vertex and Merck. Donald Jensen–Consulting: Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech/Roche, Tibotec/J&J, Astex, Biotica, Vertex, Gilead/Pharmasset, Inhibitex, Merck; Grants/contracts: research: Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech/Roche, Tibotec/J&J; Other interests: Consensus Medical Communications, Clinical Care Options. Naoky Tsai–Grants: Roche, Beckman; Consulting and advisory arrangements: Roche. Speakers' bureau: Roche. Ryan Taylor–Grants: Roche; Speakers' bureau: Roche. Alnoor Ramji - Grants, consulting, advisory arrangements, and speakers' bureau: Gilead, Merck, Hoffmann, Vertex, and Janssen. Curtis Cooper–Grants: Roche, Merck, Vertex; Advisory arrangements: Roche, Merck; Speakers' bureau: Vertex. John M. Vierling–Advisory arrangements: Abbott, Bristol-Myers Squibb, Excalenz, Gilead, Globeimmune, HepQuant, Hyperion, Immuron, Janssen, Novartis, Roche, Schering (now Merck), Salix, Sundise, Vertex, HepaLife Technologies, Herbalife, Ocera; Speakers' bureau: Chronic Liver Diseases Foundation; Grants/contracts: research: Abbott, Bristol-Myers Squibb, Conatus, Excalenz, Gilead, Globeimmune, Hyperion, Idenix-Novartis, Ikaria, Intercept, Merck (formerly Schering), Mochida, Novartis, Ocera, Pfizer, Pharmasset, Roche, Sundise, Vertex, Zymogenetics. Marie Lou Munson–employee of Genentech. Ya-Chi Chen–employee of Roche. Isabel Najera–Stock ownership or equity: Roche; employee of Roche; Grants: Abbott, Bristol-Myers Squibb, Excalenz, Gilead, GlobeImmune, Hyperion, Roche, Merck, Sundise, Ocera, Vertex, Conatus, Idenix-Novartis, Ikaria, Intercept, Mochida, Novartis, Pfizer, Pharmasset, and Zymogenetics; Consulting and advisory arrangments: Abbott, Bristol-Myers Squibb, Excalenz, Gilead, GlobeImmune, Hyperion, Roche, Merck, Sundise, Ocera, Vertex, Salix, HepaLife Technologies, Herbalife, and Ocera. James Thommes–Medical Director at Genentech.
JUMP-C: A randomized trial of mericitabine plus pegylated interferon alpha-2a/ribavirin for 24 weeks in treatment-naïve HCV genotype 1/4 patients
Article first published online: 24 JUN 2013
Copyright © 2013 American Association for the Study of Liver Diseases
Volume 58, Issue 2, pages 514–523, August 2013
How to Cite
Pockros, P. J., Jensen, D., Tsai, N., Taylor, R., Ramji, A., Cooper, C., Dickson, R., Tice, A., Kulkarni, R., Vierling, J. M., Lou Munson, M., Chen, Y.-C., Najera, I., Thommes, J. and on behalf of the JUMP-C Investigators (2013), JUMP-C: A randomized trial of mericitabine plus pegylated interferon alpha-2a/ribavirin for 24 weeks in treatment-naïve HCV genotype 1/4 patients. Hepatology, 58: 514–523. doi: 10.1002/hep.26275
This research was funded by F. Hoffmann-La Roche Ltd. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd.
Additional JUMP-C Investigators are listed in the Appendix.
See Editorial on Page 488
- Issue published online: 29 JUL 2013
- Article first published online: 24 JUN 2013
- Accepted manuscript online: 28 JAN 2013 12:56PM EST
- Manuscript Accepted: 2 JAN 2013
- Manuscript Revised: 24 DEC 2012
- Manuscript Received: 28 SEP 2012
Mericitabine is a selective nucleoside analog inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase, with activity across all HCV genotypes. Treatment-naïve patients infected with HCV genotype 1 or 4 were randomized to 24 weeks of double-blind treatment with either mericitabine 1,000 mg (N = 81) or placebo (N = 85) twice-daily (BID) in combination with pegylated interferon alpha-2a (Peg-IFNα-2a)/ribavirin (RBV). Patients randomized to mericitabine with HCV RNA <15 IU/mL from week 4 to 22 (extended rapid virologic response; eRVR) stopped all treatment at week 24; all other patients continued Peg-IFNα-2a/RBV to complete 48 weeks of treatment. The primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <15 IU/mL after 24 weeks of treatment-free follow-up). SVR was achieved in 56.8% (95% confidence interval [CI]: 45.9-67.0) of mericitabine-treated patients and 36.5% (95% CI: 27.0-47.1) of placebo-treated patients (Δ = 20.3%; 95% CI 5.5-35.2). SVR rates were higher in mericitabine- than placebo-treated patients when subdivided by IL28B genotype (CC, 77.8% versus 56.0%; non-CC, 44.1% versus 16.2%) and hepatic fibrosis (noncirrhotic, 63.3% versus 41.9%; cirrhotic, 38.1% versus 21.7%). Overall relapse rates were 27.7% and 32.0% in mericitabine- and placebo-treated patients, respectively. No evidence of NS5B S282T-variant virus or phenotypic resistance to mericitabine was observed in the one patient who experienced partial response. No S282T variants were detected in any baseline samples. The safety profile of mericitabine was similar to that of, and fewer patients in the mericitabine than in the placebo group discontinued treatment for safety reasons. Conclusion: A 24-week response-guided combination regimen of mericitabine 1,000 mg BID plus Peg-IFNα-2a/RBV is well tolerated and more effective than a standard 48-week course of Peg-IFNα-2a/RBV. (HEPATOLOGY 2013;58:514–523)