Table.

Ongoing Phase 3 Clinical Trials for NASH

Drug name	Indication	Name of trial (ClinicalTrials.gov identifier)	Number of participants	Time to endpoint	Primary endpoints
FXR agonist
Obeticholic acid	NASH F2-F3 by NASH CRN	REGENERATE (NCT02548351)	~2500	18 months	At least 1 stage of liver fibrosis improvement with no worsening of NASH or NASH resolution with no worsening of liver fibrosis
Selective THR-β agonist
Resmetirom	NASH F2-F3 by NASH CRN	MAESTRO-NASH (NCT03900429)	966 ~1700	52 weeks 54 months	Resolution of NASH (ballooning 0, inflammation 0-1) associated with at least 2-point reduction in NAS without worsening of fibrosis stage or Proportion with at least 1-stage improvement in fibrosis with no worsening of NAS Composite clinical outcome is composed of all-cause mortality, liver transplant, and significant hepatic events (including hepatic decompensation events [ascites, hepatic encephalopathy, or variceal hemorrhage], histologic progression to cirrhosis, and a confirmed increase of MELD score from <12 to ≥15)
	NAFLD/NASH diagnosed by NITs or prior biopsy	MAESTRO-NAFLD1 (NCT04197479)	~1400	52 weeks	The effect of once-daily, oral administration of 80 or 100 mg of resmetirom vs placebo on the incidence of adverse events
	Participation and completion of MAESTRONAFLD1	MAESTRO-NAFLDOLE (NCT04951219)	~1400	52 weeks	The effect of once-daily, oral administration of 80 or 100 mg of resmetirom vs placebo on the incidence of adverse events
	NASH diagnosed by NITs or prior biopsy	MAESTRO-NASHOUTCOMES (NCT05500222)	~700	52 weeks	Any event of all-cause mortality, liver transplant, ascites, hepatic encephalopathy, variceal hemorrhage, and confirmed increase of MELD score from <12 to ≥15 owing to liver disease
GLP-1 analog
Semaglutide	NASH F2-F3 by NASH CRN	ESSENCE (NCT04822181)	~1200	72 weeks 72 weeks 240 weeks	Improvement of steatohepatitis and no worsening of liver fibrosis Improvement in liver fibrosis and no worsening of steatohepatitis Time to first liver-related clinical event (composite endpoint)
PPAR-α, -γ, and -δ agonist
Lanifibranor	NASH F2-F3 by SAF score	NATiV3 (NCT04849728)	~1000	72 weeks 120 weeks	Part A: Resolution of NASH and improvement of fibrosis at week 72, defined by NASH CRN scores for ballooning of 0 and inflammation of 0-1, and fibrosis score ≥1 stage decrease compared with baseline Part B: To assess the safety of lanifibranor for 48 weeks after completion of Part A

CRN, Clinical Research Network; FXR, farnesoid X receptor; GLP-1, glucagon-like peptide-1; MELD, Model for End-Stage Liver Disease; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD Activity Score; NASH, nonalcoholic steatohepatitis; NITs, noninvasive tests; PPAR, peroxisome proliferator– activated receptor; SAF, Steatosis, Activity, and Fibrosis; THR, thyroid hormone receptor.