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.

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

BRUNETTO, MAURIZIA ROSSANA;
2013-01-01

Abstract

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.
2013
Propel, Investigators; Thommes, J; Najera, I; Chen, Yc; Munson, Ml; Ipe, D; Vierling, J; Pockros, P; Bzowej, N; Rodriguez Torres, M; Zeuzem, S; Ma, Mm; Ferenci, P; Herring, R; Jensen, D; Wedemeyer, H; Agarwal, K; Andreone, P; Benhamou, Y; Berg, T; Bloomer, J; Bronowicki, J; Brunetto, MAURIZIA ROSSANA; Bruno, S; Calleja, Jl; Iglesias, Ma; Cheng, W; Ciancio, A; Clark, V; Crawford, D; de Lédinghen, V; Desmond, P; Diago, M; Dikopoulos, N; Freilich, B; Godofsky, E; Hassanein, T; Hézode, C; Jacobson, I; Klass, Dm; Kuo, A; Lee, Ss; Leggett, B; Macdonald, Ga; Mac Quillan, G; Marotta, P; Vila, R; Pol, S; Ramji, A; Rasenack, Jw; Ratziu, V; Roberts, S; Romero Gómez, M; Rosenberg, W; Rossaro, L; Salmeron, Fj; Sánchez Tapias, Jm; Sanyal, Aj; Scuteri, A; Sepe, T; Sheikh, A; Sherman, M; Simon, Gl; Slim, J; Smith, Jp; Solà, R; Strasser, Si; Strohecker, J; Sulkowski, M; Tran, A; Willems, B; Yoshida, E; Zachoval, R; Zarski, J. .
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/844294
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