Efficacy and Safety of HSK31679 in Asian Patients With MASLD: A Randomized Controlled Trial

BACKGROUND & AIMS: This study evaluated the efficacy and safety of the thyroid hormone receptor β agonist HSK31679 in Asian patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This was a phase 2a, multicenter, randomized, double-blind, placebo-controlled study at 26 centers in China. Subjects with a liver fat content (LFC) of ≥8% at screening, when assessed by magnetic resonance imaging-proton density fat fraction, were eligible. Subjects were randomly assigned in a 1:1:1:1:1 ratio using a centralized randomization system to receive daily oral HSK31679 40 mg, HSK31679 80 mg, HSK31679 160 mg, ezetimibe 10 mg, or placebo. The primary endpoint was a relative change from baseline in LFC after 12 weeks of treatment. RESULTS: A total of 210 participants were randomly assigned to placebo (n = 42), HSK31679 40 mg (n = 42), HSK31679 80 mg (n = 42), HSK31679 160 mg (n = 42), or ezetimibe (n = 42). At week 12, the mean relative change from baseline in LFC was -4.1% in the placebo group, -14.0% in the 40 mg group (mean difference vs placebo -9.9% [95% confidence interval (CI), -21.5% to 1.6%]; P = .092), -22.7% in the 80 mg group (-18.6% [95% CI, -30.2% to -7.0%]; P = .002), and -29.2% in the 160 mg group (-25.2% [95% CI, -36.8% to -13.5%]; P < .001). The most common treatment-emergent adverse event was diarrhea (11 [26.2%] of patients in the 40 mg group, 13 [31.0%] in the 80 mg group, 16 [38.1%] in the 160 mg group, and 2 [4.8%] in the placebo group). No drug-related serious adverse events or grade ≥3 adverse events were reported. CONCLUSIONS: In Asian MASLD patients, HSK31679 was well tolerated, with significant reductions in LFC after 12 weeks of treatment with 80 mg and 160 mg. CLINICALTRIALS: gov, Number: NCT05795517.