Author information
1 Hôpital Pitié Salpêtrière and Sorbonne Université, Paris, France.
2 Department of Gastroenterology, Virginia Commonwealth University, Richmond, VA, USA.
3 Pinnacle Clinical Research, San Antonio, TX, USA.
4 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, the People's Republic of China.
5 Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
6 Center for Liver Diseases, Inova Fairfax Medical Campus, Falls Church, VA, USA.
7 NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
8 Liver Care Network, Swedish Medical Center, Seattle, WA, USA.
9 Allergan plc, South San Francisco, CA, USA.
10 Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
11 NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
12 Division of Gastroenterology & Hepatology, Department of Medicine, Duke University, Durham, NC, USA.
13 Department of Medicine III, University Hospital Aachen, Aachen, Germany.
14 Department of Gastroenterology & Hepatology, Charité University Medical Center Berlin, Berlin, Germany.
Abstract
Cenicriviroc (CVC) is a CCR2/5 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. This was a randomized, controlled study of adults with NASH, nonalcoholic fatty liver disease activity score ≥4, and NASH CRN 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, 242 participants 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 vs. 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 vs. 17% Arm C). In patients with fibrosis responses, we observed consistent reductions in PRO-C3 levels and ELF scores, while increases in APRI and FIB-4 scores were consistently observed in non-responders. Safety profile was comparable across groups. Conclusions: CVC was well-tolerated, and Year 2 data corroborates antifibrotic findings from Year 1. Majority on CVC who achieved fibrosis response at Year 1 maintained it at Year 2, with greater effect in advanced fibrosis.