Table 2.
Selected compounds under investigation for NAFLD/NASH, acting on macrophages and innate immunity components.
| Compound | Molecular target | Study population | Primary outcome | Trial number | Trial status/results |
|---|---|---|---|---|---|
| Phase III | |||||
| Cenicriviroc (AURORA) | CCR2/5 inhibitor | Histological NASH with stage F2-F3 fibrosis | Improvement in fibrosis without worsening NASH | NCT03028740 | Recruiting |
| Selonsertib (STELLAR-3) | ASK-1 inhibitor | Histological NASH with stage F3 fibrosis | Improvement in fibrosis without worsening NASH | NCT03053050 | Active, not recruiting |
| Selonsertib (STELLAR-4) | ASK-1 inhibitor | Histological NASH cirrhosis | Improvement in fibrosis without worsening NASH | NCT03053063 | Active, not recruiting |
| Phase II | |||||
| Emricasan (Encore-NF) | Caspase inhibitor | Histological NASH with stage F1-F3 fibrosis | Improvement in fibrosis without worsening NASH | NCT02686762 | Active, not recruiting |
| Emricasan (Encore-LF) | Caspase inhibitor | NASH cirrhosis + history of variceal bleeding and/or moderate/severe ascites | Event-free survival | NCT03205345 | Active, not recruiting |
| Emricasan (Encore-PH) | Caspase inhibitor | NASH cirrhosis with HVPG > 12 mm | Change in HVPG | NCT02960204 | Active, not recruiting |
| GR-MD-02 (NASH-CX) | Galectin-3 inhibitor | Compensated NASH cirrhosis with HVPG > 6 mm | Improvement in HVPG | NCT02462967 | Completed |
| IMM-124E | Polyclonal anti-LPS | Histological NASH | Improvement in liver fat content on MRI | NCT02316717 | No significant changes in liver fat content, decreased serum ALT and LPS |
| JKB-121 | TLR4 antagonist | Histological NASH | Improvement in liver fat content on MRI and/or serum ALT | NCT02442687 | No significant differences compared to placebo |
| SGM-1019 | Inflammasome inhibitor | Histological NASH with stage F1-F3 fibrosis | Safety and tolerability | NCT03676231 | Recruiting |
| Phase II trials with drug combinations | |||||
| Cenicriviroc + Tropifexor (TANDEM) | CCR2/5 inhibitor + FXR agonist | Histological NASH with stage F2-F3 fibrosis | Safety; improvement in fibrosis | NCT03517540 | Recruiting |
| Selonsertib + GS-0976 + GS-9674 (ATLAS) | ASK-1 inhibitor + ACC inhibitor + FXR agonist | Histological NASH with stage F3-F4 fibrosis or Fibroscan stiffness value ≥14.5 kPa or ELF™ score ≥ 9.8 | Safety; improvement in fibrosis without worsening NASH | NCT03449446 | Active, not recruiting |
ALT, alanine aminotransferase; ELF, Enhanced Liver Fibrosis; HVPG, hepatic venous pressure gradient; LPS, lipopolysaccharide; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.