Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis

Table 2 Phase 3 trials in non-alcoholic steatohepatitis

Trial name/NCT number	Manufacturer	Drugs	Mechanism of action	Enrollment (targeted)	Study arms	Duration (weeks)	Primary or relevant end point(s)	Results
REGENERATE/NCT02548351	Intercept Pharmaceuticals	Obeticholic acid	Farnesoid X receptor agonist	2480	(1) Obeticholic acid 10 mg QD; (2) Obeticholic acid 25 mg QD; and (3) Placebo	72-378	Fibrosis improvement (≥ 1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis	Fibrosis improvement endpoint-(12%) placebo, (18%) obeticholic acid 10 mg, (23%) obeticholic acid group 25 mg. Safety most common adverse event was pruritus
RESOLVE-IT/NCT02704403	Genfit	Elafibranor	PPAR agonist	2157	(1) Elafibranor 120 mg QD; and (2) Placebo	72-216	Change in fibrosis. Change in histologic score of NASH	ongoing
ARMOR/NCT0410432	Galmed pharmaceuticals	Aramchol	SCD-1 inhibitor	247	(1) Aramchol 600 mg QD; (2) Aramchol 400 mg qd; and (3) Placebo	364	(1) Evaluate the safety and efficacy as measured with % change in the liver triglycerides concentration; and (2) Safety	Ongoing
AURORA/NCT03028740	Tobira Therapeutics	Cenicriviroc	Dual antagonist of CCR types 2 and 5	2000	(1) Cenicriviroc 150 mg; and (2) Placebo	364	(1) Proportion of subjects with ≥ 1-stage improvement in liver fibrosis and no worsening of steatohepatitis at month 12 relative to screening; and (2) Safety	Ongoing
MAESTRO-NASH/ NCT03900429	Madrigal Pharmaceuticals	Resmetirom	Selective thyroid hormone receptor-β agonist	2000	(1) resmetirom 80 mg QD; (2) resmetirom 100 mg QD; and (3) Placebo	364	NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score-biopsy), and with no worsening of fibrosis. Secondary end p. (1) Liver fibrosis improvement of at least one stage, with no worsening of NASH; and (2) Lowering of LDL-cholesterol	Ongoing
NAVIGATE/NCT04365868	Galectin Therapeutics	GR-MD-02 (belapectin)	Inhibitor of galectin 3	1010	(1) Belapectin 2 mg/kg intravenously (IV) every other week; (2) Belapectin 4 mg/kg intravenously (IV) every other week; and (3) Placebo	504	Development of new esophageal varices at 78 weeks in the belapectin group Cumulative incidence rate of decompensations and event-free survival by time to first cirrhosis related clinical event	Ongoing

PPAR: Peroxisome proliferator-activated receptor; SCD-1: Steroyl-CoA desaturase 1; CCR: C-C motif chemokine receptor