NCT07037459招募中3 期
A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Maridebart Cafraglutide on Mortality and Morbidity in Participants Living With Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (MARITIME-HF)
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
- 5,056
- 试验地点
- 1,123
- 主要终点
- Time to First Occurrence of a Composite Endpoint Consisting of: CV Death or HF Events
研究概览
简要总结
This trial will examine if maridebart cafraglutide as an adjunct to standard of care will lead to a reduction in heart failure (HF) events such as HF hospitalizations and urgent HF visits, cardiovascular (CV) deaths and improvement in HF symptoms in participants with HF with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF) who are obese. This is a phase 3, global, multicenter, 2-part trial with a double-blind period and an open-label extension (OLE). The trial is event-driven, and Part 1 will conclude when approximately 850 primary endpoint events have occurred.
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
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of informed consent.
- •BMI ≥ 30.0 kg/m^2 at randomization.
- •HF diagnosed for at least 30 days with New York Heart Association (NYHA) Class II-IV at the time of informed consent.
- •Managed with HF standard of care therapies.
- •Left ventricular ejection fraction (LVEF) of > 40% within 12 months before randomization.
排除标准
- •History of any of the following within 60 days prior to or during screening: Type I (spontaneous) MI, valvular replacement or repair, coronary revascularization, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke.
- •HF due to: hypertrophic cardiomyopathy, infiltrative cardiomyopathy, active or chronic myocarditis, constrictive pericarditis, cardiac tamponade, arrhythmogenic right ventricular or left ventricular cardiomyopathy/dysplasia, uncorrected primary valvular heart disease, clinically significant congenital heart disease.
- •Hospitalized with acute decompensated HF at the time of or during the screening period.
- •Type 1 diabetes mellitus, or any type of diabetes with the exception of T2DM or history of gestational diabetes.
- •For participants with a prior diagnosis of T2DM (including those diagnosed during screening):
- •HbA1c > 10.0% (86 mmol/mol) at screening
- •Uncontrolled diabetes requiring immediate therapy
- •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 or presence of either proliferative diabetic retinopathy, or diabetic maculopathy, or severe non-proliferative diabetic retinopathy; or currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema.
- •SBP ≥ 180 mmHg during the screening period, or on three or more blood pressure-lowering drugs with a SBP > 160 mmHg during the screening period (including day 1 prior to randomization).
- •History of chronic pancreatitis or acute pancreatitis in the 180 days before screening or during the screening period.
- •Any personal lifetime history of, or family history(first-degree relative[s]) of medullary thyroid carcinoma or MEN-
- •eGFR < 20 mL/min/1.73 m^2 (CKD-EPI creatinine (Cr)-cystatin C equation) or receiving dialysis at screening.
- •Calcitonin ≥ 50 ng/L (pg/mL) at screening.
- •Acute or chronic hepatitis.
- •Any of the following psychiatric history:
- •History of unstable major depressive disorder or other severe psychiatric disorder within 2 years prior to screening or during the screening period
- •Lifetime history of suicide attempt
- •History of non-suicidal self-injury within 5 years prior to screening or during the screening period.
- •History of any other condition that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the trial.
- •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 prior to or during the screening period or planned use during the conduct of the trial.
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 or HF Events
时间窗: Up to approximately 35 months
Heart Failure events include: hospitalization for HF or urgent HF visits.
次要结局
- Change from Baseline in the Hemoglobin A1c (HbA1c [%, mmol/mol]) and fasting plasma glucose (mg/dL)(Baseline and Week 72)
- Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Change from Baseline in the KCCQ Total Symptom Score (TSS) for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Total Number of HF Events Including First and Recurrent HF Events(Up to approximately 35 months)
- Time to First Event of a Composite Nephropathy Endpoint(Up to approximately 35 months)
- Change in eGFR Slope (Total)(Baseline up to approximately 35 months)
- Change in eGFR Slope (Chronic)(From 4 months up to approximately 35 months)
- Time to Onset of Type 2 Diabetes Mellitus (T2DM) in Participants with Prediabetes(Up to approximately 35 months)
- Time to the First HF Event(Up to approximately 35 months)
- Change from Baseline in the Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline and Week 72)
- Change from Baseline in the Waist Circumference (cm)(Baseline and Week 72)
- Change from Baseline in the Urine Albumin-to-creatinine Ratio (uACR)(Baseline and Week 72)
- Change from Baseline in the Hemoglobin A1c (HbA1c [%, mmol/mol]) in Participants with T2DM(Baseline and Week 72)
- Percent Change from Baseline in the High-sensitivity C Reactive Protein (hs-CRP)(Baseline and Week 72)
- Percent Change from Baseline in the Body Weight (kg)(Baseline and Week 72)
- Percent Change from Baseline in Total Cholesterol(Baseline and Week 72)
- Percent Change from Baseline in Non-high-density Lipoprotein Cholesterol (non-HDL-C)(Baseline and Week 72)
- Percent Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C), HDL-C, Triglycerides (TG), Very Low-density Lipoprotein Cholesterol (VLDL-C)(Baseline and Week 72)
- Total All-cause Hospitalizations (First and Recurrent Time to Event)(Up to approximately 35 months)
- Number of Participants Achieving ≥ 5-point Change in KCCQ-CSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Number of Participants Achieving ≥ 10-point Change in KCCQ-CSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Number of Participants Achieving an Anchor-based Change in KCCQ-CSS Score From Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Number of Participants Achieving ≥ 5-point Change in KCCQ-TSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Number of Participants Achieving ≥ 10-point Change in KCCQ-TSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Number of Participants Achieving an Anchor-based Change in KCCQ-TSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80(Baseline and Week 48)
- Time to All-cause Death(Up to approximately 35 months)
- Time to CV Death(Up to Approximately 35 Months)
- Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events(Up to approximately 35 months)
- Plasma Concentration of Maridebart Cafraglutide(Week 72)
- Change from Baseline in N-terminal Pro B Type Natriuretic Peptide (NT-proBNP)(Baseline and Week 72)
- Time to New Onset of Atrial Fibrillation (AF) or Atrial Flutter (AFL) in Participants Without a History of AF or AFL at Baseline(Baseline and up to approximately 35 months)
- Time to First Occurrence of a Composite Endpoint Consisting of: Myocardial Infarction (MI), Ischemic Stroke, CV Death (Major Adverse Cardiac Events [MACE]), or HF Events(Up to approximately 35 months)
- Change from Baseline in Body Mass Index (BMI) (kg/m^2)(Baseline and Week 72)
研究者
研究点 (1123)
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