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

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).