Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke

Phase 1

• Conditions: Dyslipidemia; MedDRA version: 21.0Level: LLTClassification code 10058110Term: DyslipidemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2018-004565-14-IS
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-06
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12000

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 < 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

-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 atherosclerosic 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. lipoprotein (a) > 125 nmol/L (50 mg/dL)
6. known familial hyp

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 < 3 months prior to screening
- Uncontrolled or recurrent ventricular tachycardia in the absence of an implantable-cardioverter defibrillator.
- Atrial fibrillation 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
- Fasting triglycerides = 500 mg/dL (5.7 mmol/L) at screening
- End stage renal disease (ESRD), defined as an eGFR < 15 mL/min/1.73 m2 or receiving dialysis at screening

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