A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of HSK31679 in Patients With Metabolic Dysfunction Associated Steatohepatitis (MASH)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 886
- 试验地点
- 1
- 主要终点
- Number of Participants With Resolution of Steatohepatitis Without Worsening of Fibrosis at Week 52.
研究概览
简要总结
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) .
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 < F
- •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.
排除标准
- •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.
研究组 & 干预措施
HSK31679 dose
HSK31679 tablet, orally, once daily
干预措施: HSK31679 (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Resolution of Steatohepatitis Without Worsening of Fibrosis at Week 52.
时间窗: Week 52
Resolution of steatohepatitis is defined as total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1). Worsening of fibrosis is defined as progression of fibrosis by ≥1 stage.
Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of Steatohepatitis at Week 52.
时间窗: Week 52
Worsening of steatohepatitis is defined as increase in non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) for ballooning, inflammation, or steatosis.
Time to First Occurrence of Disease Progression
时间窗: Up to 4.5 years
Final analysis of the time to first occurrence of disease progression will be measured by a composite of protocol-specified clinical events
次要结局
未报告次要终点