A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Retatrutide on the Incidence of Major Adverse Cardiovascular Events and Major Adverse Kidney Events in Participants With Body Mass Index ≥27 kg/m2 and Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 10,000
- 试验地点
- 1,438
- 主要终点
- Time to First Occurrence of Composite Endpoints
研究概览
简要总结
The main purpose of this study is to determine if retatrutide can significantly lower the incidence of serious heart-related complications or prevent the worsening of kidney function. The trial will enroll adults with body mass index 27 kg/m^2 or higher and Atherosclerotic Cardiovascular Disease and/or chronic kidney disease. The study will last for about 5 years. Participants will have up to 27 clinic visits with the study doctor.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants may be without type 2 diabetes (T2D), or with T2D if their hemoglobin A1c (HbA1c) is 10% or lower
- •Participants have established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD), as evidenced at least one of the following:
- •Coronary artery disease
- •Cerebrovascular disease
- •Peripheral arterial disease
- •Chronic kidney disease defined as:
- •eGFR <45 millilitres/minute/1.73 meter squared (mL/min/1.73m^2) and UACR >30 milligram/gram (mg/g) (0.030 mg/mg)
- •eGFR <60 mL/min/1.73 m^2 and UACR >100 mg/g (0.100 mg/mg), or
- •eGFR <75 mL/min/1.73 m^2 and UACR >300 mg/g (0.300 mg/mg) (eGFR is calculated by central lab based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin c equation as determined by central lab)
- •A Body Mass Index of ≥27.0 kilograms per meter squared (kg/m^2)
排除标准
- •Diabetes related:
- •Participants have Type 1 Diabetes or any history of diabetic ketoacidosis
- •CV related:
- •Participants have any of the following cardiovascular conditions ≤ 90 days prior to randomization:
- •Myocardial infarction
- •Acute coronary syndrome
- •Stroke, or
- •Coronary, peripheral, or carotid artery arterial revascularization procedure.
- •Have acute decompensated heart failure requiring hospitalization.
- •Have New York Heart Association (NYHA) Classification Class IV heart failure at screening
- •Kidney related:
- •Participants have an eGFR <20 mL/min/1.73 m^2 at screening
- •Have UACR >5000 mg/g (5.000 mg/mg) at screening
- •Have received any form of dialysis ≤ 90 days from the date of randomization
- •Have either undergone a kidney transplant or have a transplant procedure scheduled
- •Other medical conditions:
- •Participants have had or plan to have a surgical treatment for obesity,
- •Have a history of chronic or acute pancreatitis
- •Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome type 2
- •Have a known clinically significant gastric emptying abnormality, such as severe gastroparesis or gastric outlet obstruction
研究组 & 干预措施
Placebo
Participants will receive matching placebo administered SC.
干预措施: Placebo (Drug)
Retatrutide
Participants will receive escalated doses of retatrutide administered subcutaneously (SC) up to a maximum tolerated dose.
干预措施: Retatrutide (Drug)
结局指标
主要结局
Time to First Occurrence of Composite Endpoints
时间窗: Randomization up to Study Completion (Approximate 248 Weeks)
A composite endpoint includes nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular (CV) death, or hospitalization or urgent visit due to heart failure (HF).
Time to First Occurrence of Composite Endpoint of End Stage Kidney Disease (ESKD), ≥ 40% Sustained Decline in Estimated Glomerular Filtration Rate (eGFR), CV Death or Renal Death
时间窗: Randomization up to Study Completion (Approximate 248 Weeks)
ESKD is defined as the following individual components: persistent eGFR \<15 mL/min/1.73 m\^2 confirmed by 2 measurements at least 4 weeks apart at the central laboratory, initiation of dialysis for at least 28 days, receiving a kidney transplant. Sustained decline in eGFR (≥40%) will be confirmed by a repeated measure at least 4 weeks after the first result.
Time to First Occurrence of Composite Endpoints
时间窗: Randomization up to Study Completion (Approximate 248 Weeks)
A composite endpoint includes nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular (CV) death, or hospitalization or urgent visit due to heart failure (HF).
Time to First Occurrence of Composite Endpoint of End Stage Kidney Disease (ESKD), ≥ 40% Sustained Decline in Estimated Glomerular Filtration Rate (eGFR), CV Death or Renal Death
时间窗: Randomization up to Study Completion (Approximate 248 Weeks)
ESKD is defined as the following individual components: persistent eGFR \<15 mL/min/1.73 m\^2 confirmed by 2 measurements at least 4 weeks apart at the central laboratory, initiation of dialysis for at least 28 days, receiving a kidney transplant. Sustained decline in eGFR (≥40%) will be confirmed by a repeated measure at least 4 weeks after the first result.
次要结局
- Time to First Occurrence of Composite Endpoint of Major Cardiovascular Events (MACE-3)(Randomization up to Study Completion (Approximate 248 Weeks))
- Time to First Occurrence of Composite Endpoint of CV death, or hospitalization or urgent visit due to HF(Randomization up to Study Completion (Approximate 248 Weeks))
- Time to Occurrence of All-Cause Death(Randomization up to Study Completion (Approximate 248 Weeks))
- Time to First Occurrence of composite endpoint of ≥ 40% Sustained Decline in eGFR, End-Stage Renal Disease (ESRD), or Renal Death(Randomization up to Study Completion (Approximate 248 Weeks))
- Percentage change from Baseline in Albuminuria urinary albumin/creatinine ratio (UACR) in Participants with UACR ≥30 mg/g (0.03 mg/mg) at baseline(Randomization up to Study Completion (Approximate 248 Weeks))