Phase II Study Evaluating the Efficacy and Safety of DR10624 Injection in MASLD and MetALD Subjects

A Randomized, Double-blind, Placebo-controlled Phase II Clinical Study Evaluating the Efficacy and Safety of DR10624 Injection in Subjects at High Risk of Liver Fibrosis With Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction and Alcohol Associated Steatotic Liver Disease

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase II clinical trial that consists of two parts. The primary objective of Part 1 is to assess the preliminary efficacy of DR10624 Injection in MASLD subjects at high risk of liver fibrosis. The secondary objectives are to assess the safety and tolerability, PK profiles, and immunogenicity of DR10624 Injection in these subjects. The exploratory objectives are to assess the efficacy of DR10624 Injection in these subjects using LSM assessed by MRE, and its impact on Lp(a) and body composition.The primary objective of Part 2 is to assess the safety and tolerability of DR10624 Injection in MetALD subjects at high risk of liver fibrosis. This clinical trial is currently only conducting Part 1 of the study.

Inclusion Criteria:

1. Subjects who have signed the informed consent form before the trial, and fully understood the trial content, process and possible adverse reactions;
2. Males or females aged 18-75 years (inclusive) at the time of signing the informed consent form;
3. LFC ≥ 10% assessed by MRI-PDFF (MRI-PDFF results that are obtained at the study site within 6 weeks prior to randomization are acceptable);
4. Screening FibroScan® with liver stiffness (LSM): ≥ 8 Kpa, and < 15 Kpa;
5. Have a body mass index (BMI) between 25.0 and 40.0 kg/m2 (inclusive) at screening;
6. Less than 5% change in body weight within 6 months prior to randomization;
7. If there is a history of type 2 diabetes, a stable treatment regimen must be maintained for at least 12 weeks prior to screening;
8. Females of childbearing potential and males must agree to use effective contraception during the study and for a specified period after the last dose of the investigational medicinal product (2 months for females, 3 months for males).

Exclusion Criteria:

1. Presence of cirrhosis on liver biopsy or imaging results, or have a history of cirrhosis;
2. Other causes of liver disease based on medical history and/or laboratory tests;
3. Previous (within 5 years before randomization) or planned (during the study period) obesity treatment with metabolic surgery or device-based therapy subjects with reversible weight-loss devices removed more than 12 months prior to randomization are eligible;
4. Type 1 diabetes;
5. History of malignancies within the last 5 years prior to screening, or malignancies that occurred more than 5 years ago but which are still currently active. Local squamous cell carcinoma of the skin or cervical intraepithelial neoplasia that has been cured without signs of recurrence is acceptable;
6. Presence of severe or uncontrolled underlying disease that, in the opinion of the investigator, renders the subject unsuitable for treatment with the investigational medicinal product or unable to complete study, or is likely to interfere with the evaluation of study results;
7. Subjects who have a history of bone trauma, fracture, or bone surgery within 2 months prior to screening, or concomitant bone disorders such as osteomalacia or known, untreated severe vitamin D deficiency (serum 25-hydroxyvitamin D ≤5 ng/mL); or a T-score ≤-2.5 for bone mineral density measured by DXA in the axial skeleton (lumbar vertebrae 1-4, femur neck, or total hip);
8. Subjects who have a history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, or a related family history;
9. Any significant abnormal laboratory findings from screening to randomization;
10. Subjects who have used or plan to use the following medications that may cause steatosis/steatohepatitis cumulatively for ≥4 weeks within 24 weeks prior to randomization or during the study: amiodarone, methotrexate, systemic corticosteroids (dose >5 mg/day prednisone equivalent), estrogens (dose greater than that used for hormone replacement therapy or contraception), tetracyclines, tamoxifen, anabolic steroids, valproic acid, or other drugs known to have hepatotoxicity, etc.;
11. Use of any of the following medications cumulatively for ≥4 weeks within 24 weeks prior to randomization or planned during the study: high-dose vitamin E (daily dose >400 IU), obeticholic acid, pioglitazone, berberine, or thyroid hormones (subjects with hypothyroidism who have received stable replacement therapy for at least 3 months prior to randomization are acceptable), etc.;
12. Use of antidiabetic drugs other than metformin, sulfonylureas, alpha-glucosidase inhibitors, glucokinase activators (GKA), or sodium-glucose cotransporter 2 (SGLT-2) inhibitors within 12 weeks prior to screening or planned during the study;
13. Use of Schisandra preparations (e.g., bifendate, bicyclol) within 6 weeks prior to randomization, or use of the following hepatoprotective drugs (including but not limited to reduced glutathione, glucuronolactone, glycyrrhizic acid preparations, polyene phosphatidylcholine, ursodeoxycholic acid, nicotinamide, liver-protecting tablets, silymarin, etc.) or other hepatoprotective Chinese proprietary medicines or health products within 2 weeks prior to randomization; or planned use of such drugs during the study;
14. Use of weight-loss drugs such as orlistat or GLP-1 receptor agonists, or other drugs with the same target as the investigational medicinal product [e.g., fibroblast growth factor-21 (FGF21) analogs, glucagon receptor (GCGR) agonists, etc.], within 6 weeks prior to screening or planned during the study;
15. Use of anti-tumor necrosis factor α (TNF-α) drugs, such as adalimumab or etanercept, etc., within 6 weeks prior to screening or planned during the study;
16. Known or suspected intolerance or hypersensitivity to the investigational medicinal product or any of its excipients; or known intolerance or hypersensitivity to drugs with the same target (e.g., FGF21 analogs, GLP-1 receptor agonists, GCGR agonists, etc.);
17. Subjects who have participated in clinical trials of other drugs and used investigational medicinal product within 12 weeks or 5 half-lives (whichever is longer) prior to screening, or those who have participated in medical device or vaccine clinical trials;
18. Alcohol consumption for at least 12 consecutive weeks within 1 year prior to screening, defined as any of the following: > 210 grams of ethanol per week for males on average, > 140 grams per week for females on average;
19. History of drug abuse or use of illicit drugs within 3 years prior to screening;
20. Pregnant or breastfeeding females, or females with a positive serum pregnancy test prior to randomization;
21. Subjects who, in the investigator's opinion, are otherwise not suitable for participation in this clinical trial.