A Trial to Evaluate the Efficacy, Safety, PK, and PD of HP515 in Non - Alcoholic Fatty Liver Disease ( NASH/MASH )

Overview

Primary Objective: • To evaluate the efficacy of HP515 tablets in participants with non-alcoholic fatty liver disease. Secondary objectives: * To evaluate the safety of HP515 tablets in participants with non-alcoholic fatty liver disease; * To evaluate the pharmacokinetic of HP515 tablets in participants with non-alcoholic fatty liver disease; * To evaluate the pharmacodynamic effects of HP515 tablets in participants with non-alcoholic fatty liver disease; Exploratory objective: • To evaluate the impact of HP515 tablets on target markers in participants with non-alcoholic fatty liver disease. The study includes a screening period of 4 weeks, a treatment period of 12 weeks, and a safety follow-up period of 4 weeks.

This study is a multicenter, randomized, double-blind, placebo-controlled Phase IIa clinical trial conducted in participants with non-alcoholic fatty liver disease. The trial includes a screening period (D-28 to D-1), a treatment period (Week 1 to Week 12), and a safety follow-up period (Week 13 to Week 16). Eligible participants are randomized based on stratification factors \\\[D1 body weight \<80 kg vs ≥80 kg\]. Participants with body weight \<80 kg are randomized in a 2:2:1 ratio to HP515 40 mg group, HP515 50 mg group, and placebo group. Participants with body weight ≥80 kg are randomized in a 2:1 ratio to HP515 60 mg group and placebo group. Each HP515 group enrolls 20 participants, totaling 60 participants, and the placebo group enrolls 20 participants, with a total of 80 participants enrolled. All participants receive 12 weeks of medication, and the entire study process includes evaluation of efficacy and safety for all participants, as well as evaluation of targeted biomarkers. All participants provided Pop-PK blood samples on an empty stomach before morning dosing at the end of Weeks 2, 6, 8, 10, and 12. Intensive blood sampling was performed for all participants completing 4 weeks of treatment or withdrawing early before the end of Week 4. Participants who completed the early withdrawal visit after at least 1 week of continuous dosing and did not discontinue medication prior to the in-person visit were encouraged to complete intensive PK sampling. ≥MRI-PDFF and FibroScan examinations were performed during the screening period, at 12 weeks of treatment, and at early withdrawal visits (requiring a minimum of 6 weeks of medication duration). Participants who completed 12 weeks of treatment completed the treatment phase, while those who completed the 16-week safety follow-up completed the trial.