NCT07037433招募中3 期
A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 12,800
- 试验地点
- 784
- 主要终点
- Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, Myocardial Infarction (MI), or Ischemic Stroke (3-point Major Adverse Cardiac Events [3-P MACE])
研究概览
简要总结
The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 45 years at screening.
- •BMI of ≥ 27.0 kg/m^2 at screening.
- •History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:
- •Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
- •Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
- •Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) < 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.
排除标准
- •History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).
- •New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.
- •Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.
- •For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):
- •HbA1c > 10.0% (86 mmol/mol) at screening.
- •History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
- •One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
- •History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.
- •Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.
- •History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.
- •Family (first-degree relative[s]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).
- •Calcitonin ≥ 50 ng/L (pg/mL) at screening.
- •Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) > 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) > 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).
- •History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).
- •Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.
研究组 & 干预措施
Maridebart Cafraglutide
Experimental
Participants will receive maridebart cafraglutide subcutaneously (SC).
干预措施: Maridebart Cafraglutide (Drug)
Placebo
Placebo Comparator
Participants will receive placebo SC.
干预措施: Placebo (Drug)
结局指标
主要结局
Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, Myocardial Infarction (MI), or Ischemic Stroke (3-point Major Adverse Cardiac Events [3-P MACE])
时间窗: Up to approximately 35 months
Time to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, MI, Ischemic Stroke, Coronary Revascularization, or Heart Failure (HF) Event (5-point MACE)
时间窗: Up to approximately 35 months
次要结局
- Change from Baseline in Fasting Plasma Glucose at Week 72(Baseline and Week 72)
- Percent Change from Baseline in High-sensitivity C-reactive protein (hs-CRP) at Week 72(Baseline and Week 72)
- Percent Change from Baseline in Body Weight at Week 72(Baseline and Week 72)
- Percent Change from Baseline in Total Cholesterol at Week 72(Baseline and Week 72)
- Percent Change from Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 72(Baseline and Week 72)
- Percent Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 72(Baseline and Week 72)
- Percent Change from Baseline in Triglycerides (TG) at Week 72(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 6.5% (48 mmol/mol) in Participants with T2DM at Baseline(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 6.0% (42 mmol/mol) in Participants with T2DM at Baseline(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 5.7% (39 mmol/mol) in Participants with T2DM at Baseline(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 6.5% (48 mmol/mol) in Participants Without T2DM at Baseline(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 6.0% (42 mmol/mol) in Participants Without T2DM at Baseline(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 5.7% (39 mmol/mol) in Participants Without T2DM at Baseline(Baseline and Week 72)
- Number of Participants at Week 72 with HbA1c < 5.7% (39 mmol/mol) in Participants with HbA1c ≥ 5.7% and < 6.5% at Baseline(Baseline and Week 72)
- Change from Baseline in Short Form 36 Health Survey Acute Version 2 (SF-36 v2) Physical Function Domain Score at Week 48(Baseline and Week 48)
- Change in eGFR (total slope) for the period from baseline to the final follow up visit(Baseline up to approximately 35 months)
- Change in eGFR (chronic slope) for the period from 4 months to the final follow-up visit(From 4 months up to approximately 35 months)
- Time to First Occurrence of MI, Ischemic Stroke or All-cause Death(Up to approximately 35 months)
- Total Major Ischemic Events (Time to First and Recurrent MI or Ischemic Stroke)(Up to approximately 35 months)
- Total All-cause Hospitalizations (Time to First and Recurrent Event)(Up to approximately 35 months)
- Time to Onset of Type 2 Diabetes Mellitus (T2DM) in Participants with Prediabetes at Baseline(Up to approximately 35 months)
- Time to Onset of T2DM in Participants without T2DM at Baseline(Up to approximately 35 months)
- Change from Baseline in Systolic Blood Pressure (SBP) at Week 72(Baseline and Week 72)
- Change from Baseline in Diastolic Blood Pressure (DBP) at Week 72(Baseline and Week 72)
- Change from Baseline in Body Mass Index (BMI) at Week 72(Baseline and Week 72)
- Change from Baseline in Urine Albumin-to-creatinine Ratio (uACR) at Week 72(Baseline and Week 72)
- Change from Baseline in Hemoglobin A1c (HbA1c) at Week 72(Baseline and Week 72)
- Time to First Event of a Composite Nephropathy Endpoint(Up to approximately 35 months)
- Change from Baseline in Waist Circumference at Week 72(Baseline and Week 72)
- Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, or HF Event(Up to approximately 35 months)
- Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke or Coronary Revascularization(Up to approximately 35 months)
- Time to First MI(Up to approximately 35 months)
- Time to First Ischemic Stroke(Up to approximately 35 months)
- Time to CV Death(Up to approximately 35 months)
- Time to All-cause Death(Up to approximately 35 months)
- Time to First Coronary Revascularization(Up to approximately 35 months)
- Time to First HF Event(Up to approximately 35 months)
- Time to First HF Event or CV Death(Up to approximately 35 months)
- Time to First Unstable Angina Requiring Hospitalization(Up to approximately 35 months)
- Time to First Occurrence of MI or CV Death(Up to approximately 35 months)
- Time to First Occurrence of a Major Adverse Limb Event (MALE) Defined as Acute Limb Ischemia, Urgent Peripheral Revascularization, Major Amputation Due to a Vascular Etiology or Chronic Limb-threatening Ischemia Requiring Revascularization(Up to approximately 35 months)
- Total Arterial (Coronary, Cerebrovascular, and Peripheral) Revascularization Procedures (Time to First and Recurrent Event)(Up to approximately 35 months)
- Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, MALE, or Arterial Revascularization(Up to approximately 35 months)
- Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, or Acute Limb Ischemia(Up to approximately 35 months)
- Time to First Occurrence of a Composite Endpoint Consisting of CV Death, MI, Ischemic Stroke, Acute Limb Ischemia, or Urgent Arterial Revascularization Procedure (Coronary, Cerebrovascular or Peripheral)(Up to approximately 35 months)
- Number of Participants with Treatment-emergent Adverse Events(Up to approximately 35 months)
- Number of Participants with Serious Adverse Events(Up to approximately 35 months)
- Plasma Concentration of Maridebart Cafraglutide at Week 72(Week 72)
研究者
研究点 (784)
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