Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis

• DOI: 10.1111/apt.13816
• Publication Date: 2016-10-25T03:26:48Z
• Authors: S. A. Harrison; S. R. Marri; N. Chalasani; R. Kohli; W. Aronstein; G. A. Thompson; W. Irish; M. V. Miles; S. A. Xanthakos; E. Lawitz; M. Noureddin; T. D. Schiano; M. Siddiqui; A. Sanyal; B. A. Neuschwande...; P. G. Traber
• Keywords: Steatohepatitis; Tolerability; Pharmacodynamics; Clinical endpoint

Background Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis prompted initiation clinical development programme fibrosis. Aim To evaluate the safety, pharmacokinetics exploratory pharmacodynamic markers GR-MD-02 subjects having bridging Methods The GT-020 study was first-in-human, sequential dose-ranging, placebo controlled, double-blinded primary objective to assess tolerability dose limiting toxicity biopsy-proven (Brunt stage 3). secondary objectives were characterise first-dose multiple-dose pharmacokinetic profiles changes serum biomarkers stiffness as assessed by FibroScan. Results single three weekly repeated 2, 4 8 mg/kg revealed no meaningful differences treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed dose-dependent relationship evidence drug accumulation following (~twofold). Conclusions doses upper range targeted therapeutic determined from pre-clinical data safe well tolerated effect. These provide support for Phase 2 due NASH.