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

dc.contributor.authorSanyal, Arun
dc.contributor.authorRatziu, Vlad
dc.contributor.authorHarrison, Stephen A
dc.contributor.authorAbdelmalek, Manal F
dc.contributor.authorAithal, Guruprasad P
dc.contributor.authorCaballeria, Juan
dc.contributor.authorFrancque, Sven
dc.contributor.authorFarrell, Geoffrey
dc.contributor.authorKowdley, Kris V
dc.contributor.authorCraxi, Antonio
dc.contributor.authorSimon, Krzysztof
dc.coverage.spatialBoston, United States
dc.date.accessioned2022-06-08T05:34:14Z
dc.date.created11-15 November
dc.date.issued2016
dc.date.updated2021-01-17T07:19:35Z
dc.description.abstractBackground: 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 observeden_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn0270-9139
dc.identifier.urihttp://hdl.handle.net/1885/267224
dc.language.isoen_AUen_AU
dc.publisherJohn Wiley & Sons Inc.en_AU
dc.relation.ispartofseries67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseasesen_AU
dc.rights© 2016 Wileyen_AU
dc.sourceHepatologyen_AU
dc.titleCenicriviroc placebo for the treatment of non-alcoholic steatohepatitis with liver fibrosis: Results from the Year 1 primary analysis of the Phase 2b CENTAUR study Abstractsen_AU
dc.typeConference paperen_AU
local.bibliographicCitation.lastpage1119Aen_AU
local.bibliographicCitation.startpage1118Aen_AU
local.contributor.affiliationSanyal, Arun, Virginia Commonwealth Universityen_AU
local.contributor.affiliationRatziu, Vlad, Marie Curie Universityen_AU
local.contributor.affiliationHarrison, Stephen A, Pinnacle Clinical Researchen_AU
local.contributor.affiliationAbdelmalek, Manal F, Duke Universityen_AU
local.contributor.affiliationAithal, Guruprasad P, University of Nottinghamen_AU
local.contributor.affiliationCaballeria, Juan, Institut d'Investigacions Biomèdiques August Pi i Sunyeren_AU
local.contributor.affiliationFrancque, Sven, University of Antwerpen_AU
local.contributor.affiliationFarrell, Geoffrey, College of Health and Medicine, ANUen_AU
local.contributor.affiliationKowdley, Kris V, Swedish Medical Centeren_AU
local.contributor.affiliationCraxi, Antonio, University of Palermoen_AU
local.contributor.affiliationSimon, Krzysztof, Wrocław Medical Universityen_AU
local.contributor.authoremailu4028700@anu.edu.auen_AU
local.contributor.authoruidFarrell, Geoffrey, u4028700en_AU
local.description.embargo2099-12-31
local.description.notesImported from ARIESen_AU
local.description.refereedYes
local.identifier.absfor111504 - Pharmaceutical Sciencesen_AU
local.identifier.absfor110307 - Gastroenterology and Hepatologyen_AU
local.identifier.absseo920199 - Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classifieden_AU
local.identifier.ariespublicationu5369653xPUB216en_AU
local.identifier.uidSubmittedByu5369653en_AU
local.publisher.urlhttps://www.wiley.com/en-gben_AU
local.type.statusPublished Versionen_AU

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