A Placebo-Controlled, Multicenter, Double-Blind, Phase 2 Randomized Trial of the Pan-Caspase Inhibitor Emricasan in Patients with Acutely Decompensated Cirrhosis

• Published in: Journal of clinical and experimental hepatology 2018-09, Vol.8 (3), p.224-234
• Main Authors: Mehta, Gautam, Rousell, Sam, Burgess, Gary, Morris, Mark, Wright, Gavin, McPherson, Stuart, Frenette, Catherine, Cave, Matthew, Hagerty, David T., Spada, Alfred, Jalan, Rajiv
• Format: Article
• Language: English
• Subjects: apoptosis; cell death; cirrhosis; liver failure; Original
• ISSN: 0973-6883; 2213-3453
• DOI: 10.1016/j.jceh.2017.11.006

Cirrhosis and acute-on-chronic liver failure (ACLF) are associated with systemic inflammation, and caspase-mediated hepatocyte cell death. Emricasan is a novel, pan-caspase inhibitor. Aims of this study were to assess the pharmacokinetics, pharmacodynamics, safety and clinical outcomes of emricasan in acute decompensation (AD) of cirrhosis. This was a phase 2, multicentre, double-blind, randomized trial. The primary objective was to evaluate the pharmacokinetics, pharmacodynamics and safety of emricasan in patients with cirrhosis presenting with AD and organ failure. AD was defined as an acute decompensating event ≤6 weeks’ duration. Patients were randomized proportionately to emricasan 5mg bid, emricasan 25mg bid, emricasan 50mg bid or placebo. Treatment was continued to 28 days, or voluntary discontinuation. Twenty-three subjects were randomized, of whom 21 were dosed (placebo n=4; 5mg n=5; 25mg n=7; 50mg n=5). Pharmacokinetic data showed 5mg dose was associated with low plasma levels (