Elevated cholesterol / Heart attack and Stroke
Conditions
Interventions
1 group receives once per 2 weeks evolocumab (140 mg/ml). The other group
receives once per 2 weeks placebo.
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: -Subject has provided informed consent prior to initiation of any study specific activities/procedures -Adult subjects >= 50 years (men) or >= 55 years (women) to = 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 µmol/L) 1. Lipid entry criteria can be measured up to 3 months prior to screening in the absence of changes to background therapy 2. Lipid criteria should be assessed after >= 2 weeks of stable, optimized lipid-lowering therapy 3. The most recent results (historical or screening) must be used -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: 1. 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 2. 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 3. 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: 1. prior transient ischemic attack with >= 50% carotid stenosis 2. internal or external carotid artery stenosis of >= 70% or 2 or more >= 50% stenoses 3. prior internal or external carotid artery revascularization C. Significant peripheral arterial disease meeting at least 1 of the following criteria: 1. >= 50% stenosis in a limb artery 2. history of abdominal aorta treatment (percutaneous and surgical) due to atherosclerotic disease 3. ankle brachial index (ABI) = 30 mg/g) and/or persistent estimated glomerular filtration rate (eGFR) = 10 years ago - At least 1 of the following high-risk criteria (most recent lab values within 6 months prior to screening, as applicable): 1. polyvascular disease, defined as coronary, carotid, or peripheral artery stenosis >= 50% in a second distinct vascular location in a patient with coronary, cerebral or peripheral arterial disease (above inclusion criterion A-C) 2. presence of either diabetes mellitus diabetes or metabolic syndrome in a subject with coronary, cerebral, or peripheral artery disease (above inclusion criterion A-C) 3. at least 1 coronary, carotid, or peripheral artery residual stenosis of >= 50% in a patient with diabetes meeting abo
Exclusion criteria
Exclusion criteria: Subjects are excluded from the study if any of the following criteria apply: 1. Disease Related - MI or stroke prior to randomization - CABG = 500 mg/dL (5.7 mmol/L) measured up to 3 months prior to screening. The most recent results must be used. - End stage renal disease (ESRD), defined as an eGFR < 15 mL/min/1.73 m2 or receiving dialysis measured up to 6 months prior to screening. The most recent results must be used. 3. Other Medical Conditions - Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years prior to day 1 - History or evidence of clinically significant disease (eg, malignancy, respiratory, gastrointestinal, renal or psychiatric disease) or unstable disorder that, in the opinion of the investigator(s), Amgen physician or designee would pose a risk to the patient*s safety or interfere with the study assessments, procedures, completion, or result in a life expectancy of less than 1 year - Persistent acute liver disease or hepatic dysfunction, defined as Child Pugh score of C 4. Prior/Concomitant Therapy - Previously received a cholesterol ester transfer protein (CETP) inhibitor (ie, anacetrapib, dalcetrapib, evacetrapib), mipomersen, lomitapide, or has undergone LDL-apheresis in the last 12 months prior to LDL-C screening - Previously received or receiving any other therapy to inhibit PCSK9 in the following timeframe prior to screening: (a) bococizumab at any time (b) evolocumab, alirocumab, or any other monoclonal antibody against PCSK9 within 3 months (c) inclisiran within 12 months 5. Prior/Concurrent Clinical Study Experience - Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). 6. Other Exclusions - Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of investigational product. - Subject has known sensitivity to any of the products or components to be administered during dosing. - Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator*s knowledge. - Subject is staff personnel directly involved with the study or is a family member of the investigational study staff - Female subject is pregnant, had a positive pregnancy test at screening (by a serum pregnancy test and/or urine pregnancy test), breastfeeding, or planning to become pregnant or breastfeed during treatment and for an additional 15 weeks after the last dose of investigational produ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Time to CHD death, MI, or ischemic stroke, whichever occurs first - Time to CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| - Time to MI, ischemic stroke, or any ischemia-driven arterial revascularization - Time to CHD death, MI, or any ischemia-driven arterial revascularization - Time to cardiovascular death, MI, or ischemic stroke - Time to CHD death or MI - Time to MI - Time to any ischemia-driven arterial revascularization - Time to CHD death - Time to cardiovascular death - Time to all cause of death - Time to ischemic stroke | — |
Countries
Netherlands
Outcome results
None listed