Table 2.
Clinical trials in NASH patients with histological outcomes (phase II–III with results).
| Author [ref.] | Target | Treatment | Phase | Duration | Histological outcome measurement | |||
|---|---|---|---|---|---|---|---|---|
| NASH resolution without worsening of fibrosis | Fibrosis improvement without worsening of NASH | |||||||
| Drug (%) | Placebo (%) | Drug (%) | Placebo (%) | |||||
| Navarro [46] | Antioxidant |
Silymarin; 420 mg, 26; 700 mg, 27; PL, 25 |
2 | 48–50 week |
NAS improvement ≥2 points 19 (420 mg)/15 (700 mg) |
12 | – | – |
| Unpublished | FXR agonist |
Tropifexor (LJN452); 140 μg, 11; 200 μg, 11; PL, 11 |
2 (adaptive design) | 48 week |
NASH resolution as secondary outcome 10.5 (140 μg)/20.0 (200 μg) |
7.1 |
Secondary outcome 28.9 (140 μg) 31.4 (200 μg) |
26.2 |
| Newsome [47] | Apical sodium-dependent Bile Acid Transporter inhibitor | Volixibat (SHP626); 5 mg, 11; 10 mg, 11; 20 mg, 8; PL, 13 | 2 | 48 week (terminated at 24 week) |
NAS improvement ≥2 points 36.4 (5 mg)/18.2 (10 mg)/37.5 (20 mg) |
38.5 | – | – |
| Harrison [14] | ASK1 inhibitor |
Selonsertib (GS-4997), F3:18 mg, 322; 6 mg, 321; PL 159 F4:18 mg, 354; 6 mg, 351; PL 172 |
3 | 48 week | – | – |
F3:9.6 (18 mg) /12.1 (6 mg) F4: 14.4(18 mg)/12.8(6 mg) |
F3: 13.2 F4: 12.8 |
| Loomba [50] |
FXR agonist; ACC inhibitor; ASK1 inhibitor |
Selonsertib, 18 mg, 7; Firsocostat, 20 mg, 33; Cilofexor, 30 mg, 34; SEL + FIR, 71; SEL + CILO, 68; FIR + CILO, 67; PL, 38 | 2b | 48 week | – | – |
Selonsertib 28.6/Firsocostat 12.1/Cilofexor 11.8 SEL + FIR 15.5 SEL + CILO 19.1 FIR + CILO 20.9 |
10.5 |
| Ratziu [16] | CCR2/CCR5 antagonist |
Cenicriviroc (CVC), 150 mg, 145; PL, 144 |
2b | 52 week |
NAS improvement ≥2 points 15.9 |
18.8 |
Secondary outcome 20.0 |
10.4 |
| Sven [77] | Pan-PPAR agonist |
Lanifibranor (IVA337), 1200 mg, 83; 800 mg, 83; PL, 81 |
2b | 24 week |
SAF improvement ≥2 points 49.4 (1200 mg) 41.0 (800 mg) |
27.2 |
Secondary outcome 42.2 (1200 mg) 27.7 (800 mg) |
23.5 |
| Newsome [49] | GLP-1 receptor agonist | Semaglutide, 0.1 mg, 57; 0.2 mg, 59; 0.4 mg, 56; PL, 58 | 2 | 72 week |
NASH resolution 40.4 (0.1 mg) 35.6 (0.2 mg) 58.9 (0.4 mg) |
17.2 |
Secondary outcome 49.1 (0.1 mg) 32.2 (0.2 mg) 42.9 (0.4 mg) |
32.8 |
| Neuschwander-Tetri [21] | FXR agonist |
Obeticholic Acid, 25 mg,110; PL, 109 |
2 | 72 week |
NAS improvement ≥2 points 45.5 |
21.1 |
Secondary outcome 35.3 |
19.4 |
| Sanyal [20] |
PPARγ agonist; Antioxidants |
Pioglitazone, 30 mg, 80; Vitamin E, 800IU, 84; PL, 83 |
3 | 96 week |
NAS ≤ 3, or NAS improvement ≥2 points Pioglitazone 33.8 Vitamin E 42.9 |
19.3 |
Secondary outcome Pioglitazone 44.3 Vitamin E 41.3 |
30.6 |
| Loomba [48] | Insulin sensitizing agents | Metformin, 2000 mg, 23 | 2 | 48 week |
NAS improvement ≥3 points 34.6 |
No | – | – |
| Unpublished | PPARγ agonist | Pioglitazone, 30 mg, 18 | 2 | 48 week |
NAS improvement ≥3 points 66.7 |
No | – | – |
| Unpublished | ACC inhibitor | Aramchol, 600 mg, 98; 400 mg, 101; PL, 48 | 2b | 52 week |
Secondary outcome NASH Resolution 16.7 (600 mg)/7.5(400 mg) |
5 |
Secondary outcome 29.5 (600 mg)/21.3 (400 mg) |
17.5 |
| Sanyal [78] | SREBP inhibitor | Ethyl icosapentate, 2700 mg, 64; 1800 mg, 55; PL, 55 | 2b | 52 week |
NAS ≤ 3, or NAS improvement ≥2 points 32.7 (1800 mg) 31.3 (2700 mg) |
32.7 | – | – |
| Dasarathy [79] | Potent activators of PPARα and PPARγ agonist | Polyunsaturated fatty acids (Opti-EPA), (360 mg EPA and 240 mg DHA), 18; PL, 19 | 2 | 48 week |
NAS improvement ≥2 points 44.4 |
47.4 | – | – |
| Harrison [15] | Insulin sensitizer | MSDC-0602K, 62.5 mg, 84; 125 mg, 82; 250 mg, 86; PL, 74 | 2b | 52 week |
NAS improvement ≥2 points 29.8 (62.5 mg) 32.9 (125 mg) 39.5 (250 mg) |
29.7 |
Secondary outcome 23.8 (62.5 mg) 28 (125 mg) 29.1 (250 mg) |
|
| Ratziu [80] | Dual PPARα/δ agonist | Elafibranor (GFT505), 80 mg, 93; 120 mg, 91; PL, 92 | 2 | 52 week |
Disappearance of NASH 23 (80 mg) 21 (120 mg) |
17 | ||
FXR farnesoid X receptor, ACC acetyl-CoA carboxylase, ASK1 apoptosis signal-regulating kinase 1, PPAR peroxisome proliferator-activated receptors, CCR2/CCR5 antagonist C–C chemokine receptors type 2 and 5 dual antagonist, GLP-1 glucagon-like peptide-1, SREBP sterol response element binding protein.