Cenicriviroc placebo for the treatment of non-alcoholic steatohepatitis with liver fibrosis: Results from the Year 1 primary analysis of the Phase 2b CENTAUR study Abstracts
Date
2016
Authors
Sanyal, Arun
Ratziu, Vlad
Harrison, Stephen A
Abdelmalek, Manal F
Aithal, Guruprasad P
Caballeria, Juan
Francque, Sven
Farrell, Geoffrey
Kowdley, Kris V
Craxi, Antonio
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John Wiley & Sons Inc.
Abstract
Background: Cenicriviroc (CVC), an oral chemokine receptor
CCR2/5 antagonist, has potent anti-inflammatory and antifibrotic
activity in animal models of acute and chronic liver
diseases. Its efficacy and safety as a treatment for non-alcoholic
steatohepatitis (NASH) and liver fibrosis are being evaluated
in adults at increased risk of progression to cirrhosis (CENTAUR;
NCT02217475). Methods: Phase 2b, randomized,
double-blind, placebo-controlled, ongoing 2-year multinational
study; primary analysis at Year 1. Subjects with histologically
defined NASH, a non-alcoholic fatty liver disease activity score
(NAS) ≥4, liver fibrosis (stages 1–3 NASH CRN), and diabetes
or metabolic syndrome (MetS) were randomized to CVC
150 mg QD or placebo. NAS, resolution of steatohepatitis,
and fibrosis stage were assessed on Year 1 liver biopsies.
Markers of systemic inflammation, treatment-emergent adverse
events (TEAEs), and laboratory abnormalities were evaluated.
Results: 289 subjects were randomized: 53% female; 52%
diabetes; 72% MetS; 74% NAS ≥5; 67% fibrosis stage 2–3.
Mean BMI (SD) was 34 kg/m2 (6.5). A similar proportion in
each group achieved the NAS and resolution of steatohepatitis
endpoints (Table). Improvement in fibrosis by ≥1 stage and
no worsening of steatohepatitis was obtained in significantly
more CVC-treated subjects than placebo overall (p=0.023)
and in subgroups with histologically advanced disease characteristics.
Improvement in fibrosis by 2 stages was observed
in 11 subjects (8 CVC; 3 placebo). Seven subjects progressed
to cirrhosis (2 CVC; 5 placebo). IL-6, hs-CRP, and fibrinogen
levels were significantly decreased with CVC vs. placebo.
Drug-related, clinical TEAEs of Grade ≥2 severity occurring in
≥2% of subjects were fatigue (2.8%) and diarrhea (2.1%) for
CVC; headache (3.5%) for placebo. There were no differences
in laboratory abnormalities or premature discontinuations
between CVC and placebo. Conclusions: In the ITT population,
CVC was well tolerated and resulted in twice as many subjects
achieving ≥1 stage improvement in fibrosis and no worsening
of steatohepatitis vs. placebo, after only 1 year of treatment.
Importantly, greater treatment benefits were observed
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Hepatology
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Conference paper
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2099-12-31
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