Effect of Evolocumab on Coronary Atherosclerosis

NCT03689946 | Completed Phase 3 Results FDA Drug FDA Device

• 1 other identifier: 54274
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This study will quantify changes in coronary plaque volumes and plaque composition in patients treated with evolocumab. Previous intravascular ultrasound studies have shown that treatment with a lipid-lowering PCSK9 enzyme inhibitor, such as evolocumab, to be associated with a reduction of the fatty deposits that cause plaque in the arteries, however, it is not known how evolocumab affects specific coronary plaque types and plaque inflammation. Investigators will use quantitative assessment of non-invasive coronary computed tomography angiography (CCTA) and positron emission tomography (PET)imaging to evaluate functional changes in plaque burden, plaque composition and vascular inflammation before and after treatment with evolocumab. Investigators propose to show that patients treated with evolocumab in combination with statins demonstrate a greater reduction of coronary non-calcified plaque volume, thereby reducing the number of future cardiac events.

Conditions

Cardiovascular Disease; Hyperlipidemia

Outcome Measures

Primary Outcomes (1)

• Change in Noncalcified Coronary Artery Plaque Volume (NCPV)

  Compare NCPV in mm\^3 measured on cardiac CT images as analyzed by quantitative software between the two assessments

  baseline (pre-treatment) and 18 months after of treatment

Secondary Outcomes (1)

• Change in Plaque Composition (Total, Calcified, Low Density Non Calcified)

  baseline (pre-treatment) and 18 months after of treatment

Study Arms (1)

Evolocumab, F18-NaF PET, CCTA

EXPERIMENTAL

Evolocumab self-administration for 18 months. Baseline (pre-treatment) and follow-up 18F-NaF PET and CCTA (possible beta-blocker and nitroglycerin, if medically safe).

Drug: Evolocumab; Diagnostic Test: 18F-NaF PET; Diagnostic Test: CCTA; Drug: Omnipaque; Drug: Metoprolol; Drug: Nitroglycerin

Interventions

Evolocumab DRUG

Evolocumab: In patients without homozygous familial hypercholesterolemia (FH), evolocumab will be self-injected as follows: 140mg every 2 weeks or 420mg once a month subcutaneously. Patients with homozygous FH will be instructed to administer 420mg subcutaneously once a month by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.

Also known as: Repatha®, PCSK9 inhibitor

Evolocumab, F18-NaF PET, CCTA

18F-NaF PET DIAGNOSTIC_TEST

18F-NaF PET: Baseline (pre-treatment) and follow-up dual cardiac and respiratory-gated PET- imaging of the thoracic aorta. Dose of 250 MBq 18F-NaF intravenously.

Also known as: 18F sodium fluoride, sodium fluoride PET

Evolocumab, F18-NaF PET, CCTA

CCTA DIAGNOSTIC_TEST

CCTA: Baseline (pre-treatment) and follow-up CCTA. Bolus injection of 80-100 ml contrast (Omnipaque or Visipaque). Possible beta blocker(metoprolol)administered to achieve a target heart ≤70 beats/min (bpm) and/or 0.4 or 0.8 mg of sublingual nitroglycerin administered, if medical safe.

Also known as: Coronary computed tomography angiography

Evolocumab, F18-NaF PET, CCTA

Omnipaque DRUG

contrast agent for CCTA

Also known as: contrast

Evolocumab, F18-NaF PET, CCTA

Metoprolol DRUG

beta blocker to optimize heart rate during CCTA

Also known as: beta blocker

Evolocumab, F18-NaF PET, CCTA

Nitroglycerin DRUG

premedication for CCTA

Also known as: vasodilator

Evolocumab, F18-NaF PET, CCTA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence by CCTA of noncalcified coronary artery plaque (\>440 mm3) and thoracic aorta atherosclerosis
• On-label indications for evolocumab treatment which includes the following criteria:
• Those who have established cardiovascular disease defined as acute coronary syndrome, history of myocardial infarction, stable angina or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.

You may not qualify if:

• Creatinine \> 1.5 mg/dL prior to imaging
• History of allergy to iodine contrast agents
• Allergy to evolocumab or any other ingredients contained in study drug
• Pregnancy
• Women who are breastfeeding
• Active atrial fibrillation
• History of coronary artery bypass graft
• Inability to lie flat
• Inability or unwilling to give informed consent
• Major illness or life expectancy \<1 year
• Planned coronary revascularization or major non-cardiac surgery in the next 12 months
• Previously or currently on evolocumab

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Amgen: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Han D, Tzolos E, Park R, Gransar H, Hyun M, Friedman JD, Hayes SW, Thomson LEJ, Kwan AC, Budoff M, Shah PK, Kwiecinski J, Wetzel S, Findling C, Slomka PJ, Dey D, Tamarappoo BK, Berman DS. Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography. JACC Cardiovasc Imaging. 2025 May;18(5):589-599. doi: 10.1016/j.jcmg.2025.01.005. Epub 2025 Apr 2.

  PMID: 40178463 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Hyperlipidemias

Interventions

evolocumab; Iohexol; Contrast Media; Metoprolol; Adrenergic beta-Antagonists; Nitroglycerin; Vasodilator Agents

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Nitro Compounds; Cardiovascular Agents; Therapeutic Uses

Limitations and Caveats

1. The sample size is small, and the study population was selectively chosen based on baseline plaque burden. 2. Because inclusion criteria focused on plaque burden, the predominantly male population, known to have higher plaque burden, limits the generalizability of the findings. 3. As a single-arm study, the absence of a comparison group receiving statin only treatment or a control group receiving no treatment limits the ability to draw direct comparisons.

Results Point of Contact

• Title: Daniel Berman
• Organization: Cedars-Sinai Medical Center

daniel.berman@cshs.org

310-423-4224

Study Officials

• Daniel S. Berman, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator/Chief Nuclear Cardiology and Cardiac Imaging

Model Details: Early development, single-arm, prospective, open-label study of evolocumab injection in patients with calcified plaque in the coronary artery detected by CCTA. Fifty-five (55) evaluable subjects will be enrolled in the study.

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 1, 2018
• Study Start: March 19, 2019
• Primary Completion: January 28, 2023
• Study Completion: May 30, 2023
• Last Updated: July 17, 2024
• Results First Posted: July 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)