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A randomized, placebo‐controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis
Author(s) -
Friedman Scott L.,
Ratziu Vlad,
Harrison Stephen A.,
Abdelmalek Manal F.,
Aithal Guruprasad P.,
Caballeria Juan,
Francque Sven,
Farrell Geoffrey,
Kowdley Kris V.,
Craxi Antonio,
Simon Krzysztof,
Fischer Laurent,
MelchorKhan Liza,
Vest Jeffrey,
Wiens Brian L.,
Vig Pamela,
Seyedkazemi Star,
Goodman Zachary,
Wong Vincent WaiSun,
Loomba Rohit,
Tacke Frank,
Sanyal Arun,
Lefebvre Eric
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.29477
Subject(s) - medicine , placebo , clinical endpoint , tolerability , gastroenterology , fibrosis , nonalcoholic fatty liver disease , population , adverse effect , surrogate endpoint , steatohepatitis , randomized controlled trial , fatty liver , pathology , disease , alternative medicine , environmental health
The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double‐blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (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 (SH) and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of SH. Biomarkers of inflammation and adverse events were assessed. Full study recruitment was achieved. The primary endpoint of NAS improvement in the intent‐to‐treat population and resolution of SH 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 endpoint 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. Conclusion: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of SH compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation. (H epatology 2018;67:1754‐1767).