Effect of Evolocumab in Patients at HighCardiovascular Risk Without Prior Myocardial Infarction or Stroke

Phase 1

• Conditions: Adults at high risk of cardiovascular events without prior MI or stroke.; MedDRA version: 21.0Level: LLTClassification code: 10058110Term: Dyslipidemia Class: 10027433; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: CTIS2023-503673-38-00
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-28
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 10919

Inclusion Criteria

Subjects must be = 50 years (men) or = 55 years (women) to < 80 years of age (either sex) and meeting lipid criteria, Lipid Criteria (see Section 11.8 for permissible concomitant lipid-lowering therapy): Subjects must have an LDL-C = 90 mg/dL (= 2.3 mmol/L) OR non-high density lipoprotein (HDL)-C = 120 mg/dL (= 3.1 mmol/L) OR apolipoprotein B = 80 mg/dL (= 1.56 umol/L), Diagnostic evidence of at least 1 of the following (A - D) at screening: A. Significant coronary artery disease meeting at least 1 of the following criteria: - History of coronary revascularization with multi-vessel coronary disease as evidenced by any of the following: -(a) percutaneous coronary intervention (PCI) of 2 or more vessels, including branch arteries -(b) PCI or coronary artery bypass grafting (CABG) with residual = 50% stenosis in a separate, unrevascularized vessel, or -(c) multi-vessel CABG 5 years or more prior to screening - Significant coronary disease without prior revascularization as evidenced by either a = 70% stenosis of at least 1 coronary artery, = 50% stenosis of 2 or more coronary arteries, or = 50% stenosis of the left main coronary artery. - known coronary artery calcium score = 100 in subjects without a coronary artery revascularization prior to randomization. B. Significant atherosclerotic cerebrovascular disease meeting at least 1 of the following criteria: -prior transient ischemic attack with = 50% carotid stenosis -internal or external carotid artery stenosis of = 70% or 2 or more = 50% stenoses -prior internal or external carotid artery revascularization C. Significant peripheral arterial disease meeting at least 1 of the following criteria: - = 50% stenosis in a limb artery -history of abdominal aorta treatment (percutaneous and surgical) due to atherosclerotic disease -ankle brachial index (ABI) < 0.85 D. Diabetes mellitus with at least 1 of the following: -known microvascular disease, defined by diabetic nephropathy or treated retinopathy. Diabetic nephropathy defined as persistent microalbuminuria (urinary albumin to creatinine ratio = 30mg/g) and/or persistent estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 that is not reversible due to an acute illness -chronic daily treatment with an intermediate or long-acting insulin -diabetes diagnosis = 10 years ago, At least 1 of the following high-risk criteria (most recent lab values within 6 months prior to screening, as applicable): - polyvascular disease, defined as coronary, carotid, or periperal artery stenosis > 50% in a seocnd distinct vasuclar location in a patient with coronary, cerebral of peripheral arterial diseasse (A, B or C above). - present of either diabetes mellitus or metabolic syndrome (Section 11.9) in a subject with coronary, cerebral, or peripheral artery disease (A, B or C above) -at least 1 coronary, carotid or periperal artery residual stenosis of > 50% in a patient with daibetes meeting inclusion criterion D above) - LDL-C > 130mg/dL (> 3.36 mmol/L), OR non-HDL-C > 160 mg/dL (> 4.14 mmol/L), OR apolipoprotein B > 120 mg/dL (2.3 µmol/L) if available -lipoprotein (a) > 125 nmol/L (50 mg/dL) - known familial hypercholesterolemia -family history of premature coronary artery disease defined as an MI or CABG in the subject's father or brother at age < 55 years or an MI or CABD in the subject's monther or sister at age < 60 years -high sensitive c-reactive protein (hsCRP) > 3.0 mg/L in the absence of an acute illness - current tobacco use - > 65 ye

Exclusion Criteria

MI or stroke prior to randomization, CABG < 3 months prior to screening, eGFR < 15 mL/min/1.73 m2, Uncontrolled or recurrent ventricular tachycardia in the absence of an implantable-cardioverter defibrillator., Atrial fibrillation or atrial flutter not on anticoagulation therapy (vitamin K antagonist, heparin, low-molecular weight heparin, fondaparinux, or non-Vitamin K antagonist oral anticoagulant), Triglycerides = 500mg/dL (5.7 mmol/L) measured up to 3 months prior to screening. The most recent results must be used., Last measured left-ventricular ejection fraction < 30% or New York Heart Association (NYHA) Functional Class III/IV, Planned arterial revascularization

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified