Table 2 |.
Ongoing major clinical trials of pharmacotherapies for the treatment of NASH1
| Agent (trial name) | Primary mechanism | Major inclusion criteria | Primary outcome(s) | Estimated completion | Trial number |
|---|---|---|---|---|---|
| Phase 3 | |||||
| Cenicriviroc (AURORA) | CCR2/5 inhibitor | NASH on biopsy with stage 2 or 3 fibrosis | Improvement in fibrosis without worsening NASH | Jul 2019 | NCT03028740 |
| Elafibranor (RESOLVE-IT) | PPARα/δ ligand | NASH on biopsy with stage 1–3 fibrosis | Resolution of NASH without worsening fibrosis | Dec 2021 | NCT02704403 |
| Obeticholic acid (REGENERATE) | FXR ligand | NASH on biopsy with stage 2 or 3 fibrosis or stage 1 fibrosis with risks for progression | Resolution of NASH without worsening fibrosis or improvement in fibrosis without worsening NASH | Oct 2022 | NCT02548351 |
| Obeticholic acid (REVERSE) | FXR agonist | NASH on biopsy with stage 4 fibrosis | Improvement in fibrosis without worsening NASH | Jul 2020 | NCT03439254 |
| Selonsertib (STELLAR 3) | ASK-1 inhibitor | NASH on biopsy with stage 3 fibrosis | Improvement in fibrosis without worsening NASH | Jan 2020 | NCT03053050 |
| Selonsertib (STELLAR 4) | ASK-1 inhibitor | NASH on biopsy with stage 4 fibrosis but no ascites, HE or variceal bleeding | Improvement in fibrosis without worsening NASH | Jan 2019 | NCT03053063 |
| Phase 2 | |||||
| Aramchol (Aramchol_005) | SCD-1 inhibitor | NASH on biopsy and >5% fat by MRS | Improvement in fat by MRS | Mar 2018 | NCT02279524 |
| BMS 130-045 (LIGHT-1) | Pegylated FGF-21 | NASH on biopsy and PDFF ≥10% | Improvement in liver fat by MRI | Jan 2017 | NCT02413372 |
| EDP-505 | FXR agonist | Histologic or phenotypic NASH | Improvement in ALT | Apr 2019 | NCT03421431 |
| Emricasan (ENCORE-NF) | Caspase inhibitor | NASH on biopsy with stage 2 or 3 fibrosis or stage 1 fibrosis with risks for progression | Improvement in fibrosis without worsening NASH | Dec 2018 | NCT02686762 |
| Emricasan (ENCORE-PH) | Caspase inhibitor | NASH cirrhosis and HVPG ≥12 mmHg | Improvement in HVPG | Oct 2018 | NCT02960204 |
| Emricasan (ENCORE-LF) | Caspase inhibitor | NASH cirrhosis with history of variceal bleeding and/or moderate or severe ascites | Event-free survival | Aug 2019 | NCT03205345 |
| GR-MD-02 (NASH-CX) | Galectin-3 inhibitor | NASH cirrhosis and HVPG ≥6 mmHg | Improvement in HVPG | Oct 2017 | NCT02462967 |
| IMM-124E | Anti-LPS | NASH on biopsy | Improvement in liver fat by MRI | Oct 2017 | NCT02316717 |
| IVA337 (NATIVE) | Pan-PPARγ agonist | NASH on biopsy and SAF >2 | SAF reduction ≥2 points without worsening fibrosis | Jan2019 | NCT03008070 |
| LIK066 | SGLT1/2 inhibitor | NASH on biopsy with stage 1–3 fibrosis or clinical risks for NASH | Improvement in ALT | Apr 2019 | NCT03205150 |
| LMB-763 | FXR agonist | Histologic or phenotypic NASH | Improvement in ALT | Aug 2019 | NCT02913105 |
| MGL-3196 | THR-β agonist | NASH on biopsy with stage 1–3 fibrosis | Improvement in liver fat by MRI | Oct 2017 | NCT02912260 |
| MSDC 0602K (EMMINENCE) | mTOT inhibitor | NASH on biopsy with stage 1–3 fibrosis | NAS reduction ≥2 points without worsening fibrosis | Jul 2019 | NCT02784444 |
| NGM282 | FGF19 analog | NASH on biopsy | Improvement in liver fat by MRI | Apr 2018 | NCT02443116 |
| PF-05221304 | ACC inhibitor | NAFLD and PDFF ≥8% | Improvement in liver fat by MRI | Feb 2019 | NCT03248882 |
| SAR425899 (RESTORE) | GLP-1 and glucagon receptor agonist | NASH on biopsy and type 2 diabetes | Resolution of ballooning without worsening of fibrosis | Jul 2020 | NCT03437720 |
| Saroglitazar (EVIDENCES II) | PPARα and PPARγ agonist | NAFLD and ALT ≥ 1.5 × ULN | Improvement in ALT | Dec 2018 | NCT03061721 |
| Selonsertib + GS-0976 + GS-9674 | ASK1 inhibitor, ACC inhibitor, FXR agonist | NASH on biopsy with stage 3 or 4 fibrosis or Fibroscan stiffness value ≥ 14.5 kPa orELF ≥ 9.8 | Improvement in fibrosis without worsening NASH | Mar 2020 | NCT03449446 |
| Semaglutide | GLP-1 mimetic | NASH on biopsy with stage 1–3 fibrosis | Resolution of NASH without worsening fibrosis | Nov 2019 | NCT02970942 |
| Tropifexor (FLIGHT-FXR) | FXR agonist | NASH on biopsy with stage 1–3 fibrosis or Clinical risks for NASH | Improvement in ALT and liver fat by MRI | Dec 2018 | NCT02855164 |
| Volixibat | ASBT inhibitor | NASH on biopsy with stage 0–3 fibrosis, >5% liver fat by MRI | NAS reduction ≥2 points without worsening fibrosis | Jul 2020 | NCT02787304 |
1
Trials registered on clinicaltrials.gov as of 16 March 2018 with the following criteria: (i) include a liver-related primary endpoint; (ii) enroll more than 50 patients; (iii) enroll at more than 3 study sites; (iv) results have not been published. CCR2/5, chemokine receptors 2 and 5; HE, hepatic encephalopathy; SCD, stearoyl-CoA desaturase; MRS, magnetic resonance spectroscopy; MRI, magnetic resonance imaging; HVPG, hepatic venous pressure gradient; SAF, steatosis, activity (inflammation and ballooning), fibrosis score; SGLT, sodium-dependent glucose cotransporter; NAS, NAFLD activity score; PDFF, proton density fat fraction by magnetic resonance imaging; ULN, upper limit of normal; ASBT, apical sodium-dependent bile acid transporter; ELF, Enhanced liver fibrosis score.