Efficacy and safety study of cenicriviroc for the treatment of non-alcoholic steatohepatitis in adult subjects with liver fibrosis: CENTAUR Phase 2b study design

• Published in: Contemporary clinical trials Vol. 47; pp. 356 - 365
• Main Authors: Friedman, Scott, Sanyal, Arun, Goodman, Zachary, Lefebvre, Eric, Gottwald, Mildred, Fischer, Laurent, Ratziu, Vlad
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2016
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Cardiovascular; CCR5 Receptor Antagonists - therapeutic use; Cenicriviroc; Clinical Protocols; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Humans; Imidazoles - therapeutic use; Liver Cirrhosis - complications; Liver fibrosis; Male; Metabolic syndrome; Middle Aged; Non-alcoholic fatty liver; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic steatohepatitis; Prospective Studies; Research Design; Treatment Outcome; Type 2 diabetes mellitus; Young Adult; Non-alcoholic fatty liver; Liver fibrosis; Type 2 diabetes mellitus; Non-alcoholic steatohepatitis; Metabolic syndrome; Cenicriviroc; metabolic syndrome; type 2 diabetes mellitus; liver fibrosis; non-alcoholic fatty liver; non-alcoholic steatohepatitis
• ISSN: 1551-7144; 1559-2030; 1559-2030
• DOI: 10.1016/j.cct.2016.02.012

Non-alcoholic steatohepatitis (NASH) is often accompanied by liver fibrosis, which can progress to cirrhosis; C-C chemokine receptors type 2 and 5 (CCR2/CCR5), which mediate interactions driving inflammation and fibrosis, are promising treatment targets. Cenicriviroc (CVC), a dual-CCR2/CCR5 antagonist, has potent anti-inflammatory and antifibrotic activity in animal models; in HIV-positive subjects it reduced soluble CD14 levels, aspartate aminotransferase-to-platelet count ratio index, and non-invasive hepatic fibrosis risk scores; favorable tolerability was demonstrated in ~600 subjects. Efficacy and safety of CVC 150mg for treating NASH with liver fibrosis are being evaluated over 2years (primary endpoint at Year 1 [Y1]). Phase 2b, randomized, double-blind, placebo-controlled, multinational study (CENTAUR; NCT02217475). Adults with histological evidence of NASH, non-alcoholic fatty liver disease activity score (NAS)≥4, and liver fibrosis (stages 1–3 NASH clinical research network system) enrolled. Subjects have increased risk of progression to cirrhosis due to ≥1 characteristic: type 2 diabetes; body mass index>25kg/m2 with ≥1 feature of metabolic syndrome; bridging fibrosis and/or NAS≥5. Liver biopsy evaluation at Screening, Y1, and Year 2 (Y2). Assess histologic improvement (≥2-point in NAS with ≥1-point improvement in >1 category) without worsening of fibrosis at Y1 (primary); evaluate complete NASH resolution without worsening of fibrosis at Y2 (key secondary). CENTAUR is the first prospective study evaluating an oral agent exclusively enrolling subjects with NASH and liver fibrosis, with increased risk of developing cirrhosis. It will compare shorter versus longer CVC treatment and assess correlations between decreased inflammation and fibrosis.