Copyright ©The Author(s) 2022.
World J Gastroenterol. Sep 21, 2022; 28(35): 5129-5140
Published online Sep 21, 2022. doi: 10.3748/wjg.v28.i35.5129
Table 1 Phase 2 trials in non-alcoholic steatohepatitis
Trial name/NCT number
Mechanism of action
Enrollment (targeted)
Study arms
Primary or relevant end point(s)
NCT03976401Akero TherapeuticsAKR-001FGF 21 receptor agonist80(1) AKR-001 50 mg QD; and (2) Placebo112Change in liver fat fraction measured by MRI-PDFFOngoing
NCT0454118689bioBIO89-100FGF 21 receptor agonist90(1) BIO89-100 (QW or every 2 wk); and (2) Placebo112Change in various lab parameters TG, LDL, HDL, fasting glucose. Change in liver fat fraction measured by MRI-PDFFOngoing
NCT02097277Bristol-Myers SquibbPegbelfermin (BMS-986036)FGF 21 receptor agonist120(1) Pegbelfermin 1 mg QD; (2) Pegbelfermin 5 mg QD; (3) Pegbelfermin 20 mg QD; (4) Pegbelfermin 20 mg weekly; and (5) Placebo84Safety, tolerability, and change in HbA1c. Change in insulin sensitivity, lipids, adiponectin, and disease progression biomarkersNo significant effects of pegbelfermin versus placebo on HbA1c. Pegbelfermin 20 mg/d significantly improved high-density lipoprotein cholesterol and triglycerides. Most frequent adverse events were injection-site bruising and diarrhea
NCT01237119Novo NordiskLiraglutideGLP-1analogue52(1) Liraglutide 1.8 mg SC QD; and (2) Placebo336Resolution of NASH without worsening fibrosis 39% who received liraglutide and underwent end-of-treatment liver biopsy had resolution of definite non-alcoholic steatohepatitis compared with 9% in placebo (P = 0·019). Side efffects diarrhea and loss of appetite
NCT02970942Novo Nordisk SemaglutideGLP-1 analogue320(1) Semaglutide 0.1 mg SC QD; (2) Semaglutide 0.2 mg SC QD; (3) Semaglutide 0.4 mg SC QD; and (4) Placebo504Resolution of NASH without worsening fibrosis. Improvement in fibrosis, LFTs, A1c levelNASH resolution was achieved in 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P < 0.001 for semaglutide 0.4 mg vs placebo). Side effects including nausea, constipation, and vomiting which was higher in the 0.4-mg group
2013-004605-38Dr Falk Pharma GmbHNorursodeoxycholic acidhomologue of ursodeoxycholic acid, undergoes hepatic enrichment with hepatoprotective, anti-inflammatory, and antifibrotic activity198(1) 500 mg norursodeoxycholic acid QD; (2) 1500 mg norursodeoxycholic acid QD; and (3) Placebo112Change in ALT levelsDose-dependent reduction in ALT with norursodeoxycholic acid versus placebo, with a significant effect in the 1500 mg group (P < 0.0001). Side effects included headache, gastrointestinal disorders, and infections
COHORT 4/NCT02443116 NGM BiopharmaceuticalsAldaferminAnalog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis78(1) aldafermin 1 mg QD; and (2) Placebo168Improvement in liver fibrosis of greater or equal to one stage with no worsening of NASHAldafermin group with higher rate of liver fat content reduction compared to placebo (7.7% vs 2.7%, P = 0.02). Aldafermin produced significantly greater decrease in bile acids, liver enzymes. Fibrosis improvement without worsening NASH higher in aldafermin group (38% vs 18%, P = 0.10). NASH resolution without worsening fibrosis higher in aldafermin group (24% vs 9%, P = 0.20). Side effects include diarrhea, headache, abdominal distation and peripheral edema
ALPINE 4/NCT04210245NGM BiopharmaceuticalsAldaferminAnalog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis72(1) Aldafermin 0.3 mg QD; (2) Aldafermin 1 mg QD; (3) Aldafermin 3 mg; and (4) Placebo168Improvement in liver fibrosis of greater or equal to one stage with no worsening of NASHOngoing
FLIGHT-FXR/NCT02855164Novartis Pharmaceutical TropifexorFXR agonist152(1) TXR 140 g QD; (2) TXR 200gr QD; and (3) Placebo 84Changes in liver fat fraction, liver enzymes, body weightEnd point achieved in TXR 800 mg vs 1200 mg vs Placebo (51% vs 55% vs 34%, P = 0.001). Side effects include mild pruritus and increase in LDL
NATIVE/NCT03008070InventivaLanifibranorPPAR agonist247(1) Lanifibranor 800 mg QD; (2) Lanifibranor 1200 mg QD; and (3) Placebo168Responder analysis based on the improvement of the SAF activity scoreL800 mg vs 1200 mg vs Placebo (51% vs 55% vs 34%) P = 0.0015. SE weight gain, peripheral edema
FASCINATE-1/NCT03938246Sagimet Biosciences IncTVB-2640FASN inhibitor99(1) TVB2640 25 mg QD; (2) TVB2640 50 mg; and (3) Placebo84Change in hepatic fat fraction from baseline in subjects with NASH by proton-density fat fraction by magnetic resonance imagingDose-dependent relative changes in liver fat by MRI-PDFF were -28.2% with 50 mg (P < 0.005 vs placebo), -9.6% with 25 mg, and +4.5% with placebo. 30% relative reduction in liver fat at week 12 were 61% (P < 0.001 vs placebo)
NCT02856555Gilead SciencesFirsocostatAcetyl-coenzyme A carboxylase Inhibitor126(1) Firsocostat 20 mg QD; (2) Firsocostat 5 mg QD; and (3) Placebo84Safety and tolerability. Secondary end point efficacy (NASH improvement without fibrosis)Decrease of at least 30% from baseline in MRI-PDFF occurred in 48% of patients with 20 mg (P = 0.004), 23% given 5 mg (P = 0.43), and 15% given placebo. SE cause, abdominal pain, diarrhea
VOYAG/LBP20Viking therapeutics VK2809Thyroid beta receptor agonist, selectively cleaved in hepatic tissue45(1) VK2809 5 mg QD; (2) VK2809 10 mg QOD; (3) VK280910 mg QD; and (4) Placebo84Safety, tolerability and efficacy in reducing liver fat content and LDL < Liver fat content was 8.7% for 5 mg QD (P = 0.0014) vs 8.9% 10 mg QOD (P = 0.013) vs 10.6% for 10 mg QD (P = 0.0030), vs 1.1% for placebo. 70% in VK2809 therapy showed a ≥ 50%. Reduction in MRI-PDFF (P = 0.014)
NCT02912260Madrigal PharmaceuticalsResmetirom (MGL-3196)Selective thyroid hormone receptor-β agonist 125(1) Resmetirom 80 mg QD; and (2) Placebo252Change in liver fat fraction measured by MRI-PDFF80 mg vs placebo reduction of hepatic fat at week 12 (-32.9% vs -10.4%; P < 0·0001) and week 36 (-37.3% vs -8.5%; P < 0·0001)
NCT02784444Cirius TherapeuticsMSDC-0602KInsulin sensitizer designed to preferentially target the mitochondrial pyruvate carrier with direct binding to the transcriptional factor PPARγ392(1) MSDC-0602K 62.5 mg QD; (2) MSDC-0602K 125 mg QD; (3) MSDC-0602K 250 mg QD; and (4) Placebo364Hepatic histological and activity score improvement in either ballooning or lobular inflammationNo increase in fibrosis stage at 12 moPrimary end point placebo 29.7%, vs 62.5 mg 29.8%, vs 125 mg 32.9% vs 250 mg 39.5% (95%CI: 0.44–1.81) (95%CI: 0.60–2.48), (95%CI: 0.83–3.27)