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Purpose

This study will assess the effect of lowering low-density lipoprotein cholesterol (LDL-C) with evolocumab on major cardiovascular events in adults without a prior myocardial infarction (MI) or stroke who are at high risk of a cardiovascular event.

Condition

Eligibility

Eligible Ages
Between 50 Years and 79 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age: Adult participants ≥ 50 (men) or ≥ 55 (women) to ˂ 80 years of age (either sex) and meeting lipid criteria. - Lipid Criteria: Low-density lipoprotein cholesterol (LDL-C) ≥ 90 mg/dL (≥ 2.3 mmol/L) or non high-density lipoprotein cholesterol (non-HDL)-C ≥ 120 mg/dL (≥ 3.1 mmol/L), or apolipoprotein B ≥ 80 mg/dL (≥ 1.56 µmol/L). 3.Diagnostic evidence of at least one of the following (A-D) at screening: A.Significant coronary artery disease (CAD) meeting at least 1 of the following criteria: - History of coronary revascularization with multi-vessel coronary disease as evidenced by any of the following: 1. percutaneous coronary intervention (PCI) of 2 or more vessels, including branch arteries, 2. PCI or coronary artery bypass grafting (CABG) with residual 50% stenosis in a separate, unrevascularized vessel, or 3. 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 participants 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 m^2 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 1 high-risk criteria (most recent lab values within 6 months prior to screening, as applicable): - Polyvascular disease, defined as coronary, carotid, or peripheral artery stenosis ≥50% in a second distinct vascular location in a participant with coronary, cerebral or peripheral arterial disease (A, B, or C above). - Presence of either diabetes mellitus or metabolic syndrome in a participant with coronary, cerebral, or peripheral artery disease (A, B, or C above). - At least 1 coronary, carotid, or peripheral artery residual stenosis of ≥50% in a participant with diabetes meeting inclusion criterion (D above). - LDL-C ≥130 mg/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 participant's father or brother at age <55 years or an MI or CABG in the participant's mother 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 years of age. - Menopause before 40 years of age. - eGFR 15 to <45 mL/min/1.73 m^2. - Coronary artery calcification score ≥300 in a participant without a coronary revascularization prior to randomization.

Exclusion Criteria

  • MI or stroke prior to randomization. - CABG ˂ 3 months prior to screening. - eGFR ˂ 15 mL/min/1.73 m^2. - 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 ≥ 500 mg/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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo 		Participants will receive placebo subcutaneous injection once every 2 weeks (Q2W).
  • Drug: Placebo
    Administered subcutaneously using an autoinjector pen.
Experimental
Evolocumab 140 mg Q2W 		Participants will receive 140 mg evolocumab by subcutaneous injection Q2W.
  • Drug: Evolocumab
    Administered subcutaneously using an autoinjector pen.
    Other names:
    • AMG 145
    • Repatha

More Details

Status
Completed
Sponsor
Amgen

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.