Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke
- Conditions
- DyslipidemiaMedDRA version: 21.0Level: LLTClassification code 10058110Term: DyslipidemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-004565-14-PT
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 13000
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)
-Subjects must have an LDL-C = 100 mg/dL (= 2.6 mmol/L) or non-HDL-C = 130 mg/dL (= 3.4 mmol/L) at screening, after = 4 weeks of 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) multi-vessel percutaneous coronary intervention (PCI)
(b) PCI or coronary artery bypass grafting (CABG) with residual =50% stenosis in a separate, unrevascularized segment or vessel, or
(c) multi-vessel CABG at least 5 years 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
B. Significant atherosclerotic cerebrovascular disease meeting at least 1 of the following criteria:
1. prior transient ischemic attack with = 50% carotid stenosis
2. carotid artery stenosis of = 70% or 2 or more = 50% stenosis
3. prior 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 microalbuminuria (urinary albumin to creatinine ratio = 30mg/g) and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
2. chronic treatment with insulin
3. diabetes diagnosis = 10 years ago
- At least 1 of the following high risk criteria at screening (most recent lab values 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. diabetes or known evidence of 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 stenosis of = 50% in a patient with diabetes meeting above inclusion criterion D
4. LDL = 130 mg/dL ( = 3.4 mmol/L) or non-HDL = 160 mg/dL (> 4.2 mmol/L)
5. lipoprotein (a) > 125 nmol/L (50 mg/dL)
6. known familial hypercholesterolemia
7. 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 CABG in the subject’s mother or sister at age < 60 years
8. high sensitive c-reactive protein = 3.0 mg/dL
9. current tobacco use
10. = 65 years of age
11. menopause before 40 years of age
12. eGFR 15 to < 45 mL/min/1.73 m2
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7215
F
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, or in situ cancers of the cervix, prostate, or breast duct within 5 years prior to screening
- 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
4. Prior/Concomitant Therapy
- Previously received or receiving evolocumab or any other therapy to inhibit PCSK9
- 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
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 subject is pregnant, had a positive pregnancy test at screening, breastfeeding, or planning to become pregnant or breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product.
- 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 personal directly involved with the study or is a family member of the investigational study staff
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method