Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Hepatology Année : 2020

Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study

Résumé

Background and aims: Cenicriviroc (CVC) is a C-C chemokine receptors type 2 and 5 dual antagonist under evaluation for treating liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). Year 1 primary analysis of the 2-year CENTAUR study showed that CVC had an antifibrotic effect without impacting steatohepatitis. Herein, we report the final data from year 2 exploratory analyses. Approach and results: This was a randomized, controlled study of adults with NASH, nonalcoholic fatty liver disease activity score ≥4, and NASH Clinical Research Network stage 1-3 fibrosis. Participants in arms A and C received CVC 150 mg or placebo, respectively, for 2 years; arm B received placebo in year 1 and switched to CVC in year 2. Liver biopsy was performed at baseline, year 1, and year 2. Of 289 randomized participants, 242 entered year 2. At year 2, 24% of patients who switched to CVC and 17% who remained on placebo achieved ≥1-stage fibrosis improvement and no worsening of NASH (P = 0.37). Twice the proportion on CVC who achieved fibrosis response at year 1 maintained benefit at year 2 (60% arm A versus 30% arm C), including 86% on CVC who had stage 3 fibrosis at baseline. Over 2 years, a similar proportion on CVC or placebo achieved ≥1-stage fibrosis improvement and no worsening of NASH (15% arm A versus 17% arm C). In patients with fibrosis responses, we observed consistent reductions in levels of N-terminal type 3 collagen propeptide and enhanced liver fibrosis scores, while increases in aspartate aminotransferase-to-platelet ratio index and Fibrosis-4 scores were consistently observed in nonresponders. Safety profile was comparable across groups. Conclusions: CVC was well tolerated, and year 2 data corroborate antifibrotic findings from year 1. The majority on CVC who achieved fibrosis response at year 1 maintained it at year 2, with greater effect in advanced fibrosis. ClinicalTrials.gov number, NCT02217475 (CENTAUR).
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Dates et versions

hal-03213544 , version 1 (30-04-2021)

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Vlad Ratziu, Arun Sanyal, Stephen A Harrison, Vincent Wai-Sun Wong, Sven Francque, et al.. Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study. Hepatology, 2020, 72 (3), pp.892-905. ⟨10.1002/hep.31108⟩. ⟨hal-03213544⟩
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