Overview
A phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and tolerability of HSK31679 compared to placebo in patients with metabolic dysfunction-associated steatohepatitis (MASH) .
Description
This study has 2 parts.Participants will be assigned to Part 1 based on screening histologic (liver biopsy) criteria or non-invasive test criteria. The purpose of the first part of this study is to find out the effect of HSK31679 on MASH and liver fibrosis. Participants will be assigned to Part 2 based on non-invasive test criteria.The purpose of the second part is to find out how safe HSK31679 is in improving liver function.
Eligibility
Key Inclusion Criteria:
- 1\. Must be willing to participate in the study and provide written informed consent.
- 2.Male and female adults ≥ 18 years of age.
- 3.Have at least one cardiometabolic risk factors at screening.
- 4.MRI-PDFF fat fraction ≥8%.
- 5.Have a liver biopsy performed within 6 months prior to randomization, with histologically confirmed MASH assessed by the central laboratory; NAS score ≥ 4 points with at least 1 point each for inflammation and hepatocellular ballooning; meanwhile, CRN fibrosis stage is F2 ≤ fibrosis \< F4. If no liver biopsy data are available within 6 months prior to randomization, a liver biopsy must be completed during the screening period.
- 6.Body weight fluctuation \< 5% for at least 6 weeks before randomization.
Key Exclusion Criteria:
- 1\. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
- 2.MELD score ≥12 due to hepatic disease。
- 3.Received medication therapy that may induce MAFLD/MASH for ≥ 2 weeks within 12 months prior to liver biopsy (including historical biopsy).
- 4.Participants who had not been on stable medication with vitamin E (dose\>400 IU/day) or polyunsaturated fatty acids or ursodeoxycholic acid within 6 months prior to liver biopsy (including historical biopsy); or had not been on stable medication with thiazolidinediones (TZD), sodium-glucose cotransporter 2 (SGLT2) inhibitors, or complex oral antidiabetic (OAD) regimens (≥3 OADs) within 3 months prior to liver biopsy (including historical biopsy).
- 5.Participants who have undergone bariatric surgery (e.g., gastroplasty, Roux-en-Y gastric bypass, etc.) within 5 years prior to screening or plan to receive such surgery during the study.
- 6.HbA1c ≥ 8.0%.
- 7.Chronic liver diseases other than NASH.
- 8.Active autoimmune disease. 9.Serum ALT \> 250 U/L. 10.Active, serious medical disease with a likely life expectancy \< 2 years.
