TY - JOUR
T1 - A Randomized, Placebo-Controlled Trial of Cenicriviroc for Treatment of Nonalcoholic Steatohepatitis with Fibrosis
AU - Craxi, Antonio
AU - Loomba, Rohit
AU - Harrison, Stephen A.
AU - Friedman, Scott L.
AU - Goodman, Zachary
AU - Farrell, Geoffrey
AU - Fischer, Laurent
AU - Vest, Jeffrey
AU - Seyedkazemi, Star
AU - Melchor-Khan, Liza
AU - Vig, Pamela
AU - Wong, Vincent Wai-Sun
AU - Kowdley, Kris V.
AU - Francque, Sven
AU - Tacke, Frank
AU - Abdelmalek, Manal F.
AU - Aithal, Guruprasad P.
AU - Wiens, Brian L.
AU - Ratziu, Vlad
AU - Caballeria, Juan
AU - Lefebvre, Eric
AU - Sanyal, Arun
AU - Simon, Krzysztof
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - CVC
KW - NAFLD
KW - NASH
KW - inflammation
KW - nonalcoholic fatty liver
KW - CVC
KW - NAFLD
KW - NASH
KW - inflammation
KW - nonalcoholic fatty liver
UR - http://hdl.handle.net/10447/248218
M3 - Article
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
ER -