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

Hepatology. 2020 Sep;72(3):892-905. doi: 10.1002/hep.31108. Epub 2020 Jul 21.


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).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartate Aminotransferases / blood*
  • Biopsy / methods
  • CCR5 Receptor Antagonists / administration & dosage
  • CCR5 Receptor Antagonists / adverse effects
  • Disease Progression
  • Drug Monitoring / methods
  • Female
  • Humans
  • Imidazoles* / administration & dosage
  • Imidazoles* / adverse effects
  • Liver / pathology*
  • Liver Cirrhosis* / diagnosis
  • Liver Cirrhosis* / etiology
  • Liver Cirrhosis* / prevention & control
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease* / blood
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Patient Acuity
  • Platelet Count / methods*
  • Receptors, CCR2 / metabolism
  • Sulfoxides* / administration & dosage
  • Sulfoxides* / adverse effects
  • Treatment Outcome


  • CCR5 Receptor Antagonists
  • Imidazoles
  • Receptors, CCR2
  • Sulfoxides
  • cenicriviroc
  • Aspartate Aminotransferases

Associated data

  • ClinicalTrials.gov/NCT02217475