Table 2.

On-going combinatory phase II trials for NASH^a

Name/Trial in registry	Combination	Mechanism of action	Participant selection & duration	Primary endpoints
ELIVATE (NCT04065841)	Tropifexor plus Licogliflozin	FXR agonist & SGLTs inhibitor	380 participants, NASH with fibrosis (F2/3), 48 weeks	At least one stage of improvement in fibrosis without worsening of NASH
TANDEM (NCT03517540)	Tropifexor plus Cenicriviroc	FXR agonist & CCR2/5 antagonist	193 participants, NASH with fibrosis (F2/3), 48 weeks	Occurrence of adverse events and serious adverse events
NEXSCOT (NCT04147195)	Tropifexor plus LYS006	FXR agonist & leukotriene A4 hydrolase inhibitor	250 participants, NASH with T2D, 21 weeks	TEAEs & SAEsb
NCT04702490	MET409 plus Empagliflozin	FXR agonist & Sodium-glucose cotransporter 2 inhibitors (SGLT2i)	120 participants, NASH with T2D, 12–16 weeks	Incidence of adverse events
NCT03646292	Pioglitazone plus Empagliflozin	Thiazolidinediones (TZD) & SGLT2i	60 participants, NASH with T2D, 6 months	Liver fat change measured by MRI-PDFF
CONTROL (NCT02633956)	Obeticholic acid plus Atorvastatin	FXR agonist & HMG CoA reductase inhibitor	84 participants, NASH with fibrosis (F1–F4), 16 weeks	LDL concentration and particle size
NCT03776175c	PF-06865571 plus PF-05221304	Diacylglycerol acyltransferase 2 (DGAT2) inhibitor & acetyl CoA carboxylase (ACC) inhibitor	99 participants, NAFLD, 6 weeks	Percent change from baseline in liver fat measured by MRI-PDFF
NCT04399538	PF-06865571 plus PF-05221304	DGAT2 inhibitor & ACC inhibitor	180 participants, NAFLD, 6 weeks	Percent change from baseline in liver fat measured by MRI-PDFF
MIRNA (NCT04321031)	PF-06865571 plus PF-05221304	DGAT2 inhibitor & ACC inhibitor	450 participants, NASH with fibrosis (F2/3), 48 weeks	Resolution of NASH without worsening of fibrosis or improvement in fibrosis by 1 > /= or both
NCT03987074	Semaglutide + Cilofexor + Firsocostat	GLP1 receptor agonist & FXR agonist & ACC inhibitor	109 participants, NASH with fibrosis (F2/3), 24 weeks	TEAEs
NCT04971785	Semaglutide + (Cilofexor or/and Firsocostat)	GLP1 receptor agonist & FXR agonist & ACC inhibitor	440 participants, NASH with compensated cirrhosis (F4), 72 weeks	1. At least one stage of improvement in fibrosis without worsening of NASH 2. NASH resolution
ATLAS (NCT03449446)	Selonsertib + Firsocostat + Cilofexor	ASK1 inhibitor & ACC inhibitor & FXR agonist	395 participants, NASH with bridging fibrosis or compensated cirrhosis (F3/4), 48 weeks	TEAEs & at least one stage of improvement in fibrosis without worsening of NASH
NCT02781584	Selonsertib + Firsocostat, Cilofexor, Fenofibrate or Vascepa	ASK1 inhibitor & ACC inhibitor & FXR agonist & PPAR-α activator & icosapent ethyl	220 participants, NASH with fibrosis (F2/3), 12 weeks	TEAEs
NCT04235205	Elobixibat + Cholestyramine	Ileal bile acid transporter (IBAT) inhibitor & bile acid sequestrant	100 participants, NASH with fibrosis (F1–F3), 16 weeks	Absolute change in serum LDL-C
PUVENAFLD (NCT04198805)	Vitamin E + Omega-3 fatty acid	Antioxidant	200 participants, NAFLD, 6 months	Change in liver fat content relative to baseline
NCT04193982	Vitamin E + Saraglitazar + Lifestyle Changes	Antioxidant & PPARα/γ agonist	250 participants, NAFLD/NASH, 6 months	Change in fibrosis score
NCT05016882	NNC0194 0499 + Semaglutide + NNC0174 0833	GLP1 receptor agonist & islet amyloid polypeptide (IAPP) analogue	672 participants, NASH with fibrosis (F2–F4), 52 weeks	Improvement in liver fibrosis and no worsening of NASH
ICAN (NCT04781933)	Probiotics and Glutamine, Quercetin, Vitamin E, Curcumin, Silybin, Pectin	Complex	60 participants, NASH with fibrosis (F2/3), 52 weeks	resolution of NASH, and no worsening of fibrosis

Probiotics = Lactobacillus rhamnosus GG, Bifidobacterium breve BR03, Lactobacillus plantaru.

^aAll information summarized in this table is from www.clinicaltrials.gov, and is traceable according to NCT number.

^bTEAEs Treatment-emergent adverse events, SAEs Treatment-emergent serious adverse events.

^cThis trial was completed.