PROPEL: A randomized trial of mericitabine plus peginterferon alpha-2a/ribavirin therapy in treatment-naïve HCV genotype 1/4 patients


  • Potential conflict of interest: Heiner Wedemeyer – Consulting: Roche, MSD, Gilead, Bristol - Myers Squibb, Novartis, Transgene, Abbott, Janssen - Ciliag; Advisory arrangements: Roche, MSD, Gilead, Bristol - Myers Squibb, Novartis, Transgene, Abbott, Janssen - Ciliag; Speakers' bureau: Roche, MSD, Gilead, Bristol - Myers Squibb, Novartis, Transgene, Abbott, Janssen - Ciliag; Grants/contracts: research: Roche, MSD, Gilead, Bristol - Myers Squibb, Novartis, Transgene, Abbott, Janssen - Ciliag; Travel grants: Roche, MSD, Gilead, Bristol - Myers Squibb, Novartis, Transgene, Abbott. 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. Peter Ferenci – Consulting: Roche, Vertex, Tibotec, MSD; Advisory arrangements: Roche, Vertex, Tibotec, MSD; Speakers' bureau: Roche, MSD; Grants/contracts: unrestricted: Roche, MSD; Travel grants: Roche. Stefan Zeuzem – Consulting: Roche; Advisory arrangements: Roche; Speakers' bureau: Roche. Maribel Rodriguez - Torres – Consulting: Akros Pharmaceutical, Bristol - Myers Squibb, Genentech, Hoffman - La Roche, Inhibitex, Janssen R&D Ireland, Merck Sharp & Dohme Corp., Pharmasset, Santaris Pharma. A/S, Vertex Pharmaceutical Inc.; Grants/contracts: research: Abbott Laboratories, Akros Pharmaceutical, Anadys Pharmaceutical, Beckman Coulter, Beohringer Ingelheim, Bristol - Myers Squibb, Genetech, Gilead Pharmaceuticals, GlaxoSmithKline, Hoffman - La Roche, Human Genome Sciences, Idenix Pharmaceutical, Idera Pharmaceutical, Inhibitex, Johnson & Johnson, Merck Sharp & Dohme Corp., Mochida Pharmaceutical, Novartis, Pfizer, Pharmasset, Santaris Pharma. A/S, Scynexis, Inc., Siemens Healthcare Diagnostics, Vertex Pharmaceutical Inc., Zymogenetics. Natalie Bzowej – Consulting: Abbott, Zymogenetics; Advisory arrangements: Gilead, Vertex; Grants/contracts: research: Bristol - Myers Squibb, Eiger, Gilead, Pharmasset, Roche/Genentech, Vertex, Zymogenetics. Paul J. Pockros – Consulting: Genentech, Vertex, Merck; Advisory arrangements: Genentech, Vertex, Merck; Speakers' bureau: Genentech, Vertex, Merck; Grants/contracts: research: Genentech, Vertex; Grants/contracts: unrestricted: Genentech, Vertex, Merck. John M. Vierling – Consulting and 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. David Ipe – employee of Genentech. Marie Lou Munson – employee of Genentech. Ya - Chi Chen – employee of Roche. Isabel Najera – Stock ownership or equity: Roche; employee of Roche. James Thommes – Medical Director at Genentech.

  • 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 PROPEL Investigators are listed in the Appendix.

  • See Editorial on Page 488


Mericitabine is a nucleoside analog polymerase inhibitor of hepatitis C virus (HCV). Treatment-naïve HCV genotype 1 or 4 patients were randomized to double-blind treatment with oral mericitabine at a dosage of 500 mg twice-daily (BID) for 12 weeks (A), 1,000 mg BID for 8 (B) or 12 weeks (C and D), or placebo BID for 12 weeks (E). All patients received pegylated interferon alpha-2a (Peg-IFNα-2a; 40 kD)/ribavirin (RBV) at standard doses for 24 or 48 weeks during and after mericitabine/placebo therapy. Patients in arms A-C who maintained a virologic response (VR) (HCV RNA <15 IU/mL) from weeks 4 to 22 stopped all treatment at week 24; all other patients (arms A-E) continued Peg-IFNα-2a/RBV to complete 48 weeks. The primary outcome was sustained VR (SVR) (HCV RNA <15 IU/mL after 24 weeks of untreated follow-up; SVR-24). VR rates were higher in arms A-D than in arm E at weeks 4 and 12 overall, in patients with and without cirrhosis and in patients with CC and non-CC IL28B genotypes. However, the overall SVR-24 rate in arms D (50.6%) and E (placebo, 51.2%) was similar and those in the response-guided therapy arms A, B, and C were lower (48.8%, 42.0%, and 32.9%, respectively). No viral breakthrough or mericitabine-resistance mutations (S282T) were observed during mericitabine therapy. Conclusion: Treatment with mericitabine plus Peg-IFNα-2a/RBV for 8 or 12 weeks provided potent suppression of HCV RNA, was well tolerated, and did not select resistant variants, but did not increase SVR rates, compared to placebo. IFN-free and IFN-containing trials of mericitabine of longer treatment duration are ongoing. (HEPATOLOGY 2013;58:524–537)