TABLE 2.
Change from baseline in the primary and secondary outcome measures at week 48 in the ITT population
| Placebo (n = 56) | Aldafermin 1 mg (n = 42) | Aldafermin 3 mg (n = 55) | |
|---|---|---|---|
| Primary end point | |||
| ELF score | 0.3 (0.1) | 0.2 (0.1) | −0.1 (0.1) |
| Difference vs. placebo | — | −0.1 (0.1) | −0.5 (0.1) |
| p value vs. placebo | — | 0.31 | 0.0003 |
| Individual components of ELF | |||
| Hyaluronic acid, ng/mL | 44.1 (23.8) | 46.5 (27.1) | 29.0 (24.9) |
| Difference vs. placebo | — | 2.4 (32.7) | −15.1 (31.0) |
| p value vs. placebo | — | 0.94 | 0.63 |
| PIIINP, ng/mL | 3.2 (1.1) | 0.7 (1.3) | −2.7 (1.2) |
| Difference vs. placebo | — | −2.5 (1.7) | −5.9 (1.6) |
| p value vs. placebo | — | 0.14 | 0.0003 |
| TIMP-1, ng/mL | 17.8 (13.2) | 6.8 (15.3) | −14.9 (13.8) |
| Difference vs. placebo | — | −11.0 (18.7) | −32.7 (17.8) |
| p value vs. placebo | — | 0.56 | 0.068 |
| Secondary end points | |||
| Liver histology | |||
| Fibrosis improvement of ≥ 1 stage (NASH CRN criteria) | 15% | 21% | 23% |
| Difference vs. placebo (95% CI) | — | 7% (−10 to 24) | 8% (−8 to 23) |
| p value vs. placebo | — | 0.39 | 0.36 |
| Fibrosis improvement of ≥ 1 stage without NASH worsening | 13% | 16% | 20% |
| Difference vs. placebo (95% CI) | — | 4% (−11 to 20) | 7% (−8 to 22) |
| p value vs. placebo | — | 0.54 | 0.37 |
| Markers of target engagement | |||
| C4, ng/mL | −10.2 (2.8) | −33.8 (3.3) | −37.7 (3.0) |
| Difference vs. placebo | −23.6 (4.1) | −27.5 (3.9) | |
| p value vs. placebo | <0.0001 | <0.0001 | |
| C4, %, relative | −1.8% (7.7) | −66.8% (9.4) | −73.5% (8.5) |
| Difference vs. placebo | −65.1% (11.6) | −71.8% (11.0) | |
| p value vs. placebo | <0.0001 | <0.0001 | |
| TBA, µmol/L | 0.9 (1.8) | −4.7 (2.1) | −5.4 (1.9) |
| Difference vs. placebo | −5.6 (2.4) | −6.3 (2.2) | |
| p value vs. placebo | 0.022 | 0.0053 | |
| TBA, %, relative | 31.7% (14.7) | −35.5% (17.4) | −50.5% (15.4) |
| Difference vs. placebo | −67.3% (19.5) | −82.3% (18.1) | |
| p value vs. placebo | 0.0008 | <0.0001 | |
| Liver enzymes | |||
| ALT, U/L | −5.7 (2.3) | −19.2 (2.6) | −22.7 (2.4) |
| Difference vs. placebo | −13.5 (3.3) | −17.0 (3.1) | |
| p value vs. placebo | 0.0001 | <0.0001 | |
| ALT, %, relative | −6.3% (4.0) | −35.9% (4.7) | −41.5% (4.3) |
| Difference vs. placebo | −29.6% (5.8) | −35.2% (5.6) | |
| p value vs. placebo | <0.0001 | <0.0001 | |
| AST, U/L | −2.4 (2.1) | −9.7 (2.5) | −13.9 (2.3) |
| Difference vs. placebo | −7.3 (3.0) | −11.6 (2.9) | |
| p value vs. placebo | 0.018 | 0.0001 | |
| AST, %, relative | −0.4% (4.5) | −19.2% (5.2) | −28.3% (4.7) |
| Difference vs. placebo | −18.8% (6.4) | −27.9% (6.1) | |
| p value vs. placebo | 0.0043 | <0.0001 | |
| Fibrogenesis marker | |||
| Pro-C3, ng/mL | 12.7 (6.2) | −9.3 (7.2) | −13.1 (6.6) |
| Difference vs. placebo | −22.1 (9.1) | −25.9 (8.7) | |
| p value vs. placebo | 0.017 | 0.0034 | |
| Pro-C3, %, relative | 47.6% (19.2) | −6.3% (22.3) | −12.1% (20.3) |
| Difference vs. placebo | −54.0% (29.2) | −59.7% (27.6) | |
| p value vs. placebo | 0.067 | 0.032 | |
| Liver stiffness by FibroScan | |||
| LSM, kPa | 0.9 (1.7) | −3.2 (1.9) | −1.3 (1.8) |
| Difference vs. placebo | — | −4.1 (2.3) | −2.3 (2.2) |
| p value vs. placebo | — | 0.078 | 0.32 |
| LSM, %, relative | 15.0% (10.1) | −15.1% (11.7) | −6.3% (11.0) |
| Difference vs. placebo | — | −30.1% (14.2) | −21.3% (13.7) |
| p value vs. placebo | — | 0.036 | 0.12 |
Values are LS mean (SE) or proportions of patients (%).
Fibrosis improvement was defined as ≥1 stage decrease in NASH CRN fibrosis score; no worsening of NASH was defined as no increase in NAS for ballooning, no increase in inflammation, and no increase in steatosis.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; C4, 7alpha-hydroxy-4-cholesten-3-one; ELF, Enhanced Liver Fibrosis; ITT, intention-to-treat; LS, least-squares; LSM, liver stiffness measure; NAS, NAFLD activity score; NASH CRN, NASH clinical research network; PIIINP, N-terminal pro-peptide of type III collagen; Pro-C3, neoepitope-specific N-terminal pro-peptide of type III collagen; TBA, total bile acids.