Table 2.
Change from baseline in glycaemic and hepatic steatosis parameters, and high-sensitivity C-reactive protein at the primary analysis timepoint
| Placebo pooled, N = 27 | Vupanorsen |
|||
|---|---|---|---|---|
| 40 mg Q4W, N = 26 | 80 mg Q4W, N = 26 | 20 mg QW, N = 26 | ||
| HbA1c (%) | ||||
| Change from baseline, LSM (95% CI) | 0.19 (–0.27, 0.64) | –0.09 (–0.56, 0.37) | 0.26 (–0.22, 0.75) | 0.35 (–0.18, 0.87) |
| Change from baseline, LSM (95% CI) vs. placebo | –0.28 (–0.94, 0.38) | 0.08 (–0.59, 0.75) | 0.16 (–0.54, 0.86) | |
| P-value | 0.3995 | 0.8155 | 0.6466 | |
| HOMA-IRa | ||||
| Change from baseline, LSM (95% CI) | –0.119 (–3.47, 3.24) | –1.914 (–5.50, 1.67) | 0.141 (–3.52, 3.80) | 2.013 (–2.41, 6.44) |
| Change from baseline, LSM (95% CI) vs. placebo | –1.794 (–6.72, 3.14) | 0.260 (–4.68, 5.20) | 2.133 (–3.44, 7.70) | |
| P-value | 0.4710 | 0.9169 | 0.4484 | |
| Hepatic fat fraction (MRI-PDFF; %) | ||||
| Change from baseline, LSM (95% CI) | –1.69 (–4.09, 0.71) | –0.71 (–3.21, 1.78) | 2.39 (–0.16, 4.94) | –0.12 (–2.87, 2.64) |
| Change from baseline, LSM (95% CI) vs. placebo | 0.98 (–2.48, 4.44) | 4.09 (0.58, 7.59) | 1.57 (–2.10, 5.25) | |
| P-value | 0.5752 | 0.0230 | 0.3965 | |
| Fatty liver indexb | ||||
| Change from baseline, LSM (95% CI) | –3.50 (–8.21, 1.22) | –6.08 (–11.08, –1.09) | –9.21 (–13.99, –4.44) | –8.07 (–13.06, –3.07) |
| Change from baseline, LSM (95% CI) vs. placebo | –2.59 (–9.49, 4.31) | –5.71 (–12.43, 1.00) | –4.57 (–11.45, 2.32) | |
| P-value | 0.4583 | 0.0943 | 0.1909 | |
| Alanine aminotransferase (U/L) | ||||
| Change from baseline, LSM (95% CI) | –2.2 (–8.48, 3.99) | 4.8 (–1.75, 11.38) | 12.5 (6.30, 18.79) | 6.6 (–0.06, 13.32) |
| Change from baseline, LSM (95% CI) vs. placebo | 7.1 (–2.10, 16.22) | 14.8 (5.98, 23.59) | 8.9 (–0.36, 18.11) | |
| P-value | 0.1294 | 0.0012 | 0.0594 | |
| Aspartate aminotransferase (U/L) | ||||
| Change from baseline, LSM (95% CI) | –1.8 (–5.50, 1.93) | 3.2 (–0.71, 7.12) | 6.7 (2.93, 10.37) | 4.7 (0.77, 8.71) |
| Change from baseline, LSM (95% CI) vs. placebo | 5.0 (–0.47, 10.45) | 8.4 (3.17, 13.70) | 6.5 (1.05, 12.00) | |
| P-value | 0.0730 | 0.0020 | 0.0200 | |
| hsCRP (mg/L) | ||||
| Change from baseline, LSM (95% CI) | 0.04 (−1.08, 1.16) | −0.93 (−2.12, 027) | −0.60 (−1.74, 0.54) | −0.51 (−1.73, 0.71) |
| Change from baseline, LSM (95% CI) vs. placebo | −0.97 (−2.61, 0.68) | −0.64 (−2.24, 0.96) | −0.55 (−2.21, 1.11) | |
| P-value | 0.2467 | 0.4296 | 0.5106 | |
Primary analysis timepoint was Week 25 (Q4W dosing) and Week 27 (QW dosing). The analysis of covariance model included fixed effects for treatment and baseline as the covariate.
CI, confidence interval; HbA1c, glycosylated haemoglobin; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; hsCRP, high-sensitivity C-reactive protein; LSM, least-squares mean; MRI, magnetic resonance imaging; PDFF, proton density fat fraction; Q4W, every 4 weeks; QW, every week.
a
HOMA-IR = Insulin μIU/mL × glucose (mg/dL)/405.
b