Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C.

Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C. Research Abstract Details 

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Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C. Abstract Text:

Patrick Marcellin,Yves Horsmans,Frederik Nevens,Jean-Didier Grange,Jean-Pierre Bronowicki,Denis Vetter,Susan Purdy,Varun Garg,Leif Bengtsson,Lindsay McNair,John Alam,Patrick Marcellin,Yves Horsmans,Frederik Nevens,Jean-Didier Grange,Jean-Pierre Bronowicki,Denis Vetter,Susan Purdy,Varun Garg,Leif Bengtsson,Lindsay McNair,John Alam,

BACKGROUND/AIMS: While combination of peginterferon-alpha (PEG-IFN) and ribavirin (RBV) therapy is the current standard of care for chronic hepatitis C (CHC), only 44-51% of genotype-1 patients achieve a sustained virological response (SVR), and both agents produce treatment-limiting toxicities. In the hepatitis C virus (HCV) replicon system, merimepodib (MMPD), a novel, selective inhibitor of inosine monophosphate dehydrogenase, has shown potent antiviral effects. METHODS: This randomized, placebo-controlled, double-blind study evaluated the safety and antiviral activity of PEG-IFN-alpha2b and RBV combined with either placebo, 25mg MMPD every 12h (q12h), or 50mg MMPD q12h in interferon-alpha (IFN) and RBV nonresponders. After 24 weeks of treatment, subjects with undetectable HCV RNA were proposed to continue assigned treatment for up to 24 additional weeks. RESULTS: The PEG-IFN-alpha, RBV, and MMPD combination was well tolerated at both doses. After 24 weeks, the proportion of HCV RNA undetectable subjects was 8/11 (73%) in the 50-mg MMPD group, 2/10 (20%) in the 25-mg MMPD group, and 3/10 (30%) in the placebo group (P=0.02, Jonckheere-Terpstra test for increasing dose response). Ten subjects entered and completed an extension study, at Week 48, 2 of 2 (100%) of the 25-mg and 3 of 5 (60%) of the 50-mg subjects remained HCV RNA undetectable, compared with 3 of 3 (100%) of the placebo subjects. At Follow-up Week 24, 2 (100%) of the 25-mg , and 1 (25%) of the 50-mg subjects remained undetectable, compared with 1 (33%) of the placebo subjects. Pharmacokinetic and pharmacodynamic analyses showed a correlation between MMPD exposure and early virological response at week 12, but not with hemoglobin decreases often associated with RBV. CONCLUSIONS: In conclusion, PEG-IFN-alpha2b and RBV combined with 50 mg MMPD q12h was well tolerated and induced virological response with undetectable HCV RNA in IFN-alpha and RBV nonresponders.

Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C. Publishing Authors By Initials

P Marcellin,Y Horsmans,F Nevens,JD Grange,JP Bronowicki,D Vetter,S Purdy,V Garg,L Bengtsson,L McNair,J Alam,P Marcellin,Y Horsmans,F Nevens,JD Grange,JP Bronowicki,D Vetter,S Purdy,V Garg,L Bengtsson,L McNair,J Alam,

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Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of hepatology

VOLUME: 47

Page Numbers: 476-83

Journal Abbreviation: J. Hepatol.

ISSN: 0168-8278

DAY: 21

MONTH: 06

YEAR: 2007

Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C. Information

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LANGUAGE: eng

NlmUniqueID: 8503886

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Grant and Affiliation Information for Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C.

AFFILIATION: Hôpital Beaujon, Service d'Hépatologie, 100 Bld du General Leclerc, 92100 Clichy, France. Patrick.marcellin@bjn.ap-hop-paris.fr

Country: England

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MEDLINETA: J Hepatol

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