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. 2023 Dec 11;10:1316284. doi: 10.3389/fmed.2023.1316284

Table 1.

Glossary of clinical trials in MASLD/MASH.

Trial Type of trial Patients Intervention Duration Main findings
ALPINE 2/3 (156) 2b 171 patients with fibrotic (F1-F3) MASH Adalfermin 0.3 mg, 1.0 mg or 3 mg/day vs. placebo 24 weeks

  • Did not meet primary endpoints of histological improvement of fibrosis without worsening MASH

  • Dose–response for resolution of MASH (11, 18, and 22% vs. 6% for placebo), relative LFC (25, 38, and 59% vs. 15% for placebo), aminotransferases and ProC3
ARMOR 3 150 patients with fibrotic (F1-F3) MASH Aramchol 300 mg bid vs. placebo 52 weeks Ongoing
ARREST (157) 2b 247 patients with fibrotic (F1-F3) MASH Aramchol 400 mg or 600 mg/day vs. placebo 52 weeks

  • Did not meet primary endpoint of decrease in relative LFC

  • Did not achieve histological improvement of fibrosis without worsening MASH or MASH resolution without fibrosis worsening
BALANCED (158) 2a 80 patients with fibrotic (F1-F3) MASH Efruxifermin 28 mg, 50 mg or 70 mg/week vs. placebo 16 weeks

  • Dose–response decrease in relative LFC: 63, 71 and 72% vs. 0.3% for placebo

  • Decrease in liver enzymes and fibrosis by NIT’s (ELF and ProC3)
CENTAUR (139) 2b 171 patients with fibrotic (F1-F3) MASH Cenicriviroc 150 mg/day vs. placebo 24 months Non-significant higher proportion of patients achieved histological improvement of fibrosis without worsening MASH (2-% vs. 11%)
CONTROL (159) 2 84 patients with MASH OCA 5 mg, 10 mg or 25 mg/day + atorvastatin 10 mg/day after week 4 16 weeks OCA-induced increases in LDL-cholesterol in patients with MASH were mitigated with atovastatin
DESTINY-1 (133) 2 117 patients with fibrotic (F1-F3) MASH PXL065 7.5 mg, 15 mg, 22.5 mg/day vs. placebo 36 weeks

  • Decrease in LFC for all doses (23, 19, 21% vs. 2% increase for placebo)

  • Trend to improvement of fibrosis by NIT’s (PIIINP and NAFLD Fibrosis Score)

  • Improvement in HbA1c and insulin sensitivity. No effect on body weight
ENLIVEN (160) 2b 219 patients with fibrotic (F2-F3) MASH Pegbelfermin 15 mg or 30 mg/week or 44 mg/q2week vs. placebo 24 weeks

  • Higher proportion of fibrosis improvement without worsening of MASH (22, 26, and 27% vs. 7% for placebo), and of MASH resolution without worsening fibrosis (37, 23, and 26% vs. 2% for placebo)

  • Improvement of LFC and fibrosis by NIT’s (liver stiffness and ProC3)
ESSENCE 3 1,200 patients with fibrotic (F2-F3) MASH Semaglutide 2.4 mg/week vs. placebo 72 and 240 weeks Ongoing
FALCON-1 (161) 2b 197 patients with MASH and bridging fibrosis Pegbelfermin 10 mg, 20 mg or 40 mg/week vs. placebo 48 weeks

  • Did not meet primary endpoints of histological improvement of fibrosis without worsening MASH or MASH resolution without worsening fibrosis

  • Dose–response higher proportion of patients with decrease ≥30% MRI-PDFF and ≥ 15% MRE
FALCON-2 (162) 2b 154 patients with MASH and compensated cirrhosis Pegbelfermin 10 mg, 20 mg or 40 mg/week vs. placebo 48 weeks

  • Did not meet primary endpoints of histological improvement of fibrosis without worsening MASH or decrease in collagen proportionate area

  • No difference in the proportion of patients achieving decrease ≥30% MRI-PDFF and ≥ 15% MRE
FASCINATE-1 (163) 2a 99 patients with biopsy-confirmed MASH or LFC ≥ 8% + MRE ≥ 2.5 Denifanstat 25 mg or 50 mg/day vs. placebo 12 weeks

  • Dose–response decrease in relative LFC (10 and 28% vs. 4.5% increase for placebo)

  • Decrease in fibrosis by NITs (ProC3 and TIMP-1) only with the highest dose
FASCINATE-2 (164) 2b 168 patients with fibrotic (F1-F3) MASH Denifanstat 50 mg/day vs. placebo 26 weeks

  • Decrease in relative LFC compared with placebo (34% vs. 1.5%)

  • Decrease in fibrosis by NITs (ProC3 and ELF score)
FLIGHT-FXR (165, 166) 2 152 patients with MASH Tropifexor 140ug or 200ug/day vs. placebo 48 weeks Did not achieve histological improvement in MASH or fibrosis according to NASH-CRN scoring, but did achieve overall and perisinusoidal liver fibrosis in patients F2/F3 baseline, when assessed by digital pathology (SHG/TPEF) with artificial intelligence
FLINT (154) 2 283 patients with fibrotic (F1-F3) MASH OCA 25 mg/day vs. placebo 72 weeks

  • Higher proportion of fibrosis improvement without worsening of MASH (35% vs. 19% for placebo), and of MASH resolution without worsening fibrosis (22% vs. 13% for placebo)

  • Pruritus in almost one-fourth of the patients, worsened insulin resistance and lipid profile
GOLDEN 505 (136) 2b 276 patients with fibrotic (F1-F3) MASH Elafibranor 80 mg or 120 mg/day vs. placebo 52 weeks

  • Did not meet primary endpoints of NASH resolution without worsening fibrosis, except in a post-hoc analysis for patients with NAS ≥ 4 (13–19% vs. 9% for placebo)

  • Fibrosis improvement in elafibranor responders

  • Improved cardiometabolic risk profile
HARMONY (167) 2b Non-cirrhotic fibrotic (F1-F3) MASH Efruxifermin 28 mg or 50 mg/week vs. placebo 24 weeks

  • Dose–response higher proportion of fibrosis improvement without worsening of MASH (39 and 41% vs. 20% for placebo), and of MASH resolution without worsening fibrosis (47 and 76% vs. 15% for placebo)

  • Improvement of LFC, weight, insulin sensitivity and lipid profile
IMPACT NASH 2b 190 patients with fibrotic (F2-F3) MASH Pemvidutide 1.2 mg or 1.8 mg/week vs. placebo 24 and 48 weeks Ongoing
LEAN (82) 2 52 overweight patients with MASH Liraglutide 1.8 mg/day vs. placebo 48 weeks Compared with placebo, liraglutide associated with higher proportion of patients with MASH resolution (39% vs. 9%) and lower with fibrosis progression (9% vs. 36%)
MAESTRO- NASH (168) 3 966 patients with fibrotic (F1-F3) MASH Resmetirom 80 mg or 100 mg/day vs. placebo 52 weeks

  • Dose–response higher proportion of fibrosis improvement without worsening of MASH (24 and 26% vs. 14% for placebo), and of MASH resolution without worsening fibrosis (26 and 30% vs. 10% for placebo)

  • Improvement of LFC, fibrosis by NIT’s, liver and spleen volume
NATIVE (169) 2b 247 patients with fibrotic (F1-F3) MASH Lanifibranor 800 mg or 1,200 mg/day vs. placebo 24 weeks

  • Dose–response higher proportion of fibrosis improvement without worsening of MASH (39 and 48% vs. 29% for placebo), and of MASH resolution without worsening fibrosis (25 and 36% vs. 7% for placebo)

  • Increase in adiponectin despite weight gain
NATIV3 3 MASH + significant fibrosis (F2-F3) Lanifibranor 800 mg or 1,200 mg/day vs. placebo 72 weeks Ongoing
NAVIGATE 2/3 MASH-cirrhosis Belapectin 2 mg or 4 mg/qow vs. placebo 18 months

  • Primary endpoint is prevention of esophageal varices

  • Ongoing
PIVENS (113) 3 247 patients with fibrotic (F1-F3) MASH Pioglitazone 30 mg/day or Vitamin E 800 IU/day vs. placebo 96 weeks

  • Higher proportion of improvement in MASH in Vitamin E (43%) and Pioglitazone (35%) compared with placebo (9%)

  • Both Vitamin E and Pioglitazone failed to promote fibrosis improvement
REGENERATE (170, 171) 3 2,477 fibrotic (F1-F3) MASH OCA 10 mg or 25 mg/day vs. placebo 18 months

  • In the subgroup of 931 patients with fibrosis F2-F3, higher proportion of fibrosis improvement without worsening of MASH (14 and 22% vs. 10% for placebo), and of MASH resolution without worsening fibrosis (6% vs. 3.5% for placebo)

  • Pruritus in almost one-third of patients for 10 mg and 50% for 25 mg arms
RESOLVE-IT (137) 3 1,070 patients with fibrotic (F1-F3) MASH Elafibranor 120 mg/day vs. placebo 18 months

  • Did not meet primary endpoints of histological improvement of fibrosis without worsening MASH or MASH resolution without worsening fibrosis

  • Clinical outcomes yet to be known
REVERSE 3 919 patients with compensated MASH-associated cirrhosis OCA 10 mg or 25 mg/day vs. placebo 72 weeks

  • Did not meet primary endpoints of histological improvement of fibrosis without worsening MASH

  • Pruritus up to 57% and increased risk of gallstones
STELLAR-3/4 (140) 3 802 patients with F3 and 877 with F4 fibrosis and MASH Selonsertib 6 mg or 18 mg/day vs. placebo 48 weeks Did not meet primary endpoints of histological improvement of fibrosis without worsening MASH or MASH resolution without worsening fibrosis
SYNCHRONY 3 Patients with MASH Efruxifermin 3 clinical trials ongoing: histology, real-world, and outcomes
SYNERGY NASH study 2b 196 patients with fibrotic (F2-F3) MASH Tirzepatide 10 mg or 15 mg/week vs. placebo 52 weeks Ongoing
TESLA-NASH 2 30 obese ± MS with non-cirrhotic NASH Endoscopic sleeve gastroplasty vs. laparoscopic sleeve gastrectomy 96 weeks
VOYAGE 2b 167 patients with fibrotic (F1-F3) MASH VK2809 1 mg or 2.5 mg/day, 5 mg or 10mgqod vs. placebo 52 weeks

  • All doses resulted in a decrease in relative LFC (13, 41, 33 and 48%) at 12 weeks

  • Still ongoing evaluation of histological response at week 52

LFC, liver fat content by MRI-PDFF; MRE, magnetic resonance elastography; NASH-CRN, nonalcoholic steatohepatitis clinical research network; OCA, obethicholic acid; PXL065, deuterium-stabilized R-pioglitaxone; SHG, second harmonic generation; TPEF, two-photon excitation fluorescence.