A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis

Friedman, Scott L. and Ratziu, Vlad and Harrison, Stephen A. and Abdelmalek, Manal F. and Aithal, Guruprasad P. and Caballeria, Juan and Francque, Sven and Farrell, Geoffrey and Kowdley, Kris V. and Craxi, Antonio and Simon, Krzysztof and Fischer, Laurent and Melchor-Khan, Liza and Vest, Jeffrey and Wiens, Brian L. and Vig, Pamela and Seyedkazemi, Star and Goodman, Zachary and Wong, Vincent Wai-Sun and Loomba, Rohit and Tacke, Frank and Sanyal, Arun and Lefebvre, Eric (2017) A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology . ISSN 1527-3350 (In Press)

[img] PDF - Repository staff only until 17 August 2018. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1MB)

Abstract

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis.

A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score [NAS] ≥4, and liver fibrosis (stages 1–3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of steatohepatitis. Biomarkers of inflammation and adverse events were assessed.

Full study recruitment was achieved. The primary end point of NAS improvement in the intent-to-treat population and resolution of steatohepatitis was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144) (16% vs 19%, P = 0.52 and 8% vs 6%, P = 0.49, respectively). However, the fibrosis end point was met in significantly more subjects on CVC than placebo (20% vs 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo.

Conclusions: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of steatohepatitis compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation.

ClinicalTrials.gov no: NCT02217475 (CENTAUR).

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Friedman, S. L., Ratziu, V., Harrison, S. A., Abdelmalek, M. F., Aithal, G. P., Caballeria, J., Francque, S., Farrell, G., Kowdley, K. V., Craxi, A., Simon, K., Fischer, L., Melchor-Khan, L., Vest, J., Wiens, B. L., Vig, P., Seyedkazemi, S., Goodman, Z., Wong, V. W.-S., Loomba, R., Tacke, F., Sanyal, A. and Lefebvre, E. (), A Randomized, Placebo-Controlled Trial of Cenicriviroc for Treatment of Nonalcoholic Steatohepatitis with Fibrosis. Hepatology. Accepted Author Manuscript which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/hep.29477/abstract This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: NASH, NAFLD, CVC, nonalcoholic fatty liver, inflammation
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Nottingham Digestive Diseases Centre
Identification Number: 10.1002/hep.29477
Depositing User: Eprints, Support
Date Deposited: 21 Aug 2017 12:48
Last Modified: 13 Oct 2017 20:39
URI: http://eprints.nottingham.ac.uk/id/eprint/45019

Actions (Archive Staff Only)

Edit View Edit View