A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 4,500
- 试验地点
- 982
- 主要终点
- Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
研究概览
简要总结
The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression.
Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.
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
- Single (Participant)
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
- •Have liver fat content ≥8%
- •Have ELF score of ≥9 and ≤10.8 at screening
- •Have VCTE LSM ≥10 kilopascal (kPa) and <20 kPa at screening
排除标准
- •Have any other type of liver disease other than MASLD
- •Have a body mass index (BMI) <25 kilogram per square meter (kg/m2)
- •Prior decompensated liver disease (history of esophageal/gastric varices, ascites, hepatic encephalopathy)
- •Have lost more than 11 pounds within the 3 months prior to screening
- •Have a hemoglobin A1c (HbA1c) greater than 10%
- •Have type 1 diabetes
研究组 & 干预措施
Tirzepatide (TZ01)
Participants will receive tirzepatide subcutaneously (SC)
干预措施: Tirzepatide (Drug)
Placebo (RT01)
Participants will receive placebo SC
干预措施: Placebo (Drug)
Placebo (TZ01)
Participants will receive placebo SC
干预措施: Placebo (Drug)
Retatrutide (RT01)
Participants will receive retatrutide SC
干预措施: Retatrutide (Drug)
结局指标
主要结局
Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
时间窗: Baseline up to Study Completion (about 224 weeks)
Composite endpoint comprised of progression to cirrhosis, development of large esophageal varices, gastric varices or development of varices needing treatment, development of ascites, development of hepatic encephalopathy, evidence of active or recent variceal hemorrhage, increase in model for end-stage liver disease (MELD) from ≤12 to ≥15, liver transplantation, all-cause mortality
Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
时间窗: Baseline up to Study Completion (about 224 weeks)
Composite endpoint comprised of progression to cirrhosis, development of large esophageal varices, gastric varices or development of varices needing treatment, development of ascites, development of hepatic encephalopathy, evidence of active or recent variceal hemorrhage, increase in model for end-stage liver disease (MELD) from ≤12 to ≥15, liver transplantation, all-cause mortality
次要结局
- Change from Baseline in Enhanced Liver Fibrosis (ELF) Score(Baseline, Week 104)
- Percent Change from Baseline in Liver Fat Content (LFC)(Baseline, Week 104)
- Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK)(Baseline, Week 104)
- Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM)(Baseline, Week 104)
- Time to Occurrence of Progression to Cirrhosis(Baseline up to Study Completion (about 224 weeks))
- Change from Baseline in Aspartate Aminotransferase (AST)(Baseline, Study Completion (about 224 weeks))
- Change from Baseline in Alanine Aminotransferase (ALT)(Baseline, Study Completion (about 224 weeks))
- Change from Baseline in Body Weight(Baseline, Study Completion (about 224 weeks))
- Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3)(Baseline up to Study Completion (about 224 weeks))
- Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM)(Baseline, Week 104)
- Percent Change from Baseline in Liver Fat Content (LFC)(Baseline, Week 104)
- Time to Occurrence of Progression to Cirrhosis(Baseline up to Study Completion (about 224 weeks))
- Change from Baseline in Aspartate Aminotransferase (AST)(Baseline, Study Completion (about 224 weeks))
- Change from Baseline in Alanine Aminotransferase (ALT)(Baseline, Study Completion (about 224 weeks))
- Change from Baseline in Body Weight(Baseline, Study Completion (about 224 weeks))
- Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK)(Baseline, Week 104)
- Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3)(Baseline up to Study Completion (about 224 weeks))