A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Impact of Evolocumab on Major Cardiovascular Events in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke
- Conditions
- Elevated cholesterol / Heart attack and Stroke1008220610013317
- Registration Number
- NL-OMON54527
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 1250
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 < 80 years of age (either sex) and meeting
lipid criteria -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 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) < 0.85 D. Diabetes mellitus with at least
1 of the following: 1. known microvascular disease, defined by diabetic
nephropathy or treated retinopathy. Diabetic nephropathy defined as persistent
microalbuminuria (urinary albumin to creatinine ratio >= 30 mg/g) and/or
persistent estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 that
is not reversible due to an acute illness 2. chronic daily treatment with an
intermediate or long-acting insulin 3. 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): 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
Subjects are excluded from the study if any of the following criteria apply: 1.
Disease Related - MI or stroke prior to randomization - CABG < 3 months prior
to screening - 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) - Last measured left-ventricular ejection fraction < 30% or New
York Heart Association (NYHA) Functional Class III/IV - Planned arterial
revascularization 2. Diagnostic Assessments - Triglycerides >= 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Time to CHD death, MI, or ischemic stroke, whichever occurs first - Time to<br /><br>CHD death, MI, ischemic stroke, or any ischemia-driven arterial<br /><br>revascularization, whichever occurs first</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Time to MI, ischemic stroke, or any ischemia-driven arterial<br /><br>revascularization<br /><br>- Time to CHD death, MI, or any ischemia-driven arterial revascularization<br /><br>- Time to cardiovascular death, MI, or ischemic stroke<br /><br>- Time to CHD death or MI<br /><br>- Time to MI<br /><br>- Time to any ischemia-driven arterial revascularization<br /><br>- Time to CHD death<br /><br>- Time to cardiovascular death<br /><br>- Time to all cause of death<br /><br>- Time to ischemic stroke</p><br>