Table 3.
Anti-apoptotic, inflammatory, and fibrogenic agents under clinical trials
| Class | Drug classification | Drug name | Registered clinical trails | Outcome | Ref. |
|---|---|---|---|---|---|
| Anti-apoptotic agents | ASK1 inhibitor | Selonsertib (GS-4997) |
Phase 2 (NCT02466516) Phase 3 (NCT03053050, NCT03053063) |
↓Hepatic steatosis ↓Liver fibrosis No antifibrotic effect in patients with bridging fibrosis or compensated cirrhosis due to NASH in phase 3 trials |
321,620 |
| Pan-caspase inhibitor | Emricasan (IDN-6556) | Phase 2 (NCT02077374, NCT02230670, NCT02686762) | No effects on liver fibrosis in patients with NASH | 315–317,621 | |
| Anti-inflammatory agents | CCR2/5 antagonist | Cenicriviroc |
Phase 2b (NCT02217475) Phase 3 (NCT03028740, terminated) |
↓Liver fibrosis ↓Inflammation |
397,398 |
| Anti-TNFα drug | Pentoxyfylline (PTX) | Phase 2/3 (NCT00267670, NCT00590161) |
↓Hepatic steatosis Effects on NASH are controversial |
408–410 | |
| Antifibrosis | Antioxidant | Vitamin E |
Phase 3 (NCT00063622) Phase NA (NCT02962297) |
↓Hepatic steatosis ↓Inflammation ↓ALT, AST ↓Liver fibrosis |
284,285,622 |
| Angiotensin-II receptor blocker | Losartan | Phase 3 (NCT01051219) | No results posted | ||
| Galectin-3 (Gal-3) inhibitor | Belapectin (GR-MD-02) |
Phase 2 (NCT02462967, NCT02421094) Phase 1 (NCT01899859) |
No effects on liver fibrosis in patients with NASH | 434,623 | |
| LOXL2 antibody | Simtuzumab (SIM, GS-6624) | Phase 2b (NCT01672866, NCT01672879) | Terminated due to lack of efficacy. | 431–433 | |
| HSP47 inhibitor | BMS-986263 |
Phase 2 (NCT03420768) (EudraCT Number: 2019-003932-22) |
↓Liver fibrosis | 437 | |
| Cell therapy | Stem cell therapy | UC-MSC | Phase 1/2 (NCT01220492) |
↓ALB, PTA, CHE, TBIL ↑Survival rate in patients with decompensated liver cirrhosis |
548 |
| BM-MSC | Phase 2 (NCT01875081) | Improved histologic fibrosis and liver function in patients with alcoholic cirrhosis | 624 | ||
| Genetic approaches |
RNAi target HSD17B13 |
ARO-HSD | Phase 1 (NCT04202354) |
↓ALT, AST ↓Hepatic HSD17B13 mRNA and protein |
562 |
| ALN-HSD | Phase 1 (NCT04565717) | No results posted | |||
| ASO against PNPLA3 | ION839 (AZD2693) | Phase 1 (NCT04483947, recruiting) | No results posted | ||
| ASO against DGAT2 | IONIS-DGAT2Rx | Phase 2 (NCT03334214, NCT04932512, recruiting) | ↓Hepatic steatosis | 566 | |
| GalNAc-conjugated anti-miR-103/107 oligonucleotide | RG-125 (AZD4076) | Phase 1 (NCT02826525, NCT02612662) | No results posted | ||
| Gut microbiota | Gut microbiota targets | Probiotics | Phase NA (NCT00870012) |
↓AST ↓Hepatic TG |
530 |