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Hepatology. 2018 May;67(5):1754-1767. doi: 10.1002/hep.29477. Epub 2018 Jan 29.

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

Author information

1
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Mount Sinai, NY.
2
Pitié Salpêtrière Hospital and Pierre and Marie Curie University, Paris, France.
3
Pinnacle Clinical Research, San Antonio, TX.
4
Division of Gastroenterology & Hepatology, Department of Medicine, Duke University, Durham, NC.
5
Nottingham Digestive Diseases Centre National Institute for Health Research (NIHR) and Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
6
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
7
Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
8
Liver Research Group, Australian National University Medical School at the Canberra Hospital, Canberra, Australian Capital Territory, Australia.
9
Liver Care Network, Swedish Medical Center, Seattle, WA.
10
Department of Gastroenterology, DiBiMIS, University of Palermo, Palermo, Italy.
11
Division of Infectious Diseases and Hepatology, Faculty of Medicine and Dentistry, Wrocław Medical University, Wrocław, Poland.
12
Department of Infectious Diseases, J. Gromkowski Provincial Specialist Hospital in Wrocław, Wrocław, Poland.
13
Allergan, Plc, South San Francisco, CA.
14
Medpace, Inc., Cincinnati, OH.
15
Center for Liver Diseases, Inova Fairfax Medical Campus, Falls Church, VA.
16
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
17
Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA.
18
NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA.
19
Department of Medicine III, University Hospital Aachen, Aachen, Germany.
20
Department of Gastroenterology, Virginia Commonwealth University, Richmond, VA.

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 (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. (Hepatology 2018;67:1754-1767).

PMID:
28833331
PMCID:
PMC5947654
DOI:
10.1002/hep.29477
[Indexed for MEDLINE]
Free PMC Article

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