title: Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis.
abstract: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis.
  
  
  
  To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis.
  
  
  
  The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan.
  
  
  
  GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold).
  
  
  
  GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.
authors: Fort Sam Houston, TX, USA.
authors: S A
authors: SA
authors: Harrison
authors: Indianapolis, IN, USA.
authors: S R
authors: SR
authors: Marri
authors: Indianapolis, IN, USA.
authors: N
authors: N
authors: Chalasani
authors: Cincinnati, OH, USA.
authors: R
authors: R
authors: Kohli
authors: Cincinnati, OH, USA.
authors: W
authors: W
authors: Aronstein
authors: West Chester, OH, USA.
authors: G A
authors: GA
authors: Thompson
authors: Cincinnati, OH, USA.
authors: W
authors: W
authors: Irish
authors: Cincinnati, OH, USA.
authors: M V
authors: MV
authors: Miles
authors: Cincinnati, OH, USA.
authors: S A
authors: SA
authors: Xanthakos
authors: San Antonio, TX, USA.
authors: E
authors: E
authors: Lawitz
authors: Los Angeles, CA, USA.
authors: M
authors: M
authors: Noureddin
authors: New York, NY, USA.
authors: T D
authors: TD
authors: Schiano
authors: Richmond, VA, USA.
authors: M
authors: M
authors: Siddiqui
authors: St. Louis, MO, USA.
authors: A
authors: A
authors: Sanyal
authors: St. Louis, MO, USA.
authors: B A
authors: BA
authors: Neuschwander-Tetri
authors: Norcross, GA, USA.|Atlanta, GA, USA.
authors: P G
authors: PG
authors: Traber
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy*; D010368:Pectins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D010368:Pectins; C000613472:belapectin