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: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-004565-14-SE
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12000
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 at screening (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 above inclusion criterion D
4. 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
5. lipoprote
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 product.
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