Effect of Evolocumab on Coronary Artery Plaque Volume and Composition by CCTA and Microcalcification by F18-NaF PET

Effect of Evolocumab on Coronary Artery Plaque Volume and Composition by Coronary CTA (CCTA) and Microcalcification by F18-NaF PET: A Phase 3 Study

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Hyperlipidemia
• Intervention / Treatment: Drug: Evolocumab; Diagnostic test: 18F-NaF PET; Diagnostic test: CCTA

Detailed Description

To evaluate the effect of evolocumab, patients who are taking Evolocumab plus another cholesterol-lowering medication (e.g statins), will undergo diagnostic testing including non-invasive coronary CT angiographic (CCTA) scans and positron emission tomography (PET) scans. The CCTA and PET scans will be done before and after being treated with evolocumab.

At the initial visit, standard imaging eligibility screening will take place, as well as blood sampling to test cholesterol levels and presence of proteins (biomarkers) associated with heart disease. A CCTA will be done (if not done for clinical purposes within the past 90 days) and a PET scan with administration of 18F-NaF injection will take place. Patients will receive the first injection of evolocumab and will be taught how to self-inject once or twice a month for 18 months.

After the initial visit, patients will self-inject evolocumab at approximately 6, 12 and 18 months in front of a medical professional for site monitoring and re-training. Labs will be drawn to assess blood components related to heart disease.

Follow-up phone calls will be made at approximately 1,3, 9, 15 months and approximately 3-7 days after their final on-site visit (18 months) to monitor safety and drug adherence.

The final visit (18 months after the initial visit) will involve another PET scan, CCTA and blood collection for biomarker testing.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Evolocumab, F18-NaF PET, CCTA; 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; 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.; Other Names: PCSK9 inhibitor; Repatha®; Diagnostic test: 18F-NaF PET; 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.; Other Names: sodium fluoride PET; 18F sodium fluoride; Diagnostic test: CCTA; 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.; Other Names: Coronary computed tomography angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in noncalcified coronary artery plaque volume (NCPV)	Compare NCPV in mm3 measured on cardiac CT images as analyzed by quantitative software between the two assessments	baseline (pre-treatment) and 18 months after of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plaque composition (fibrous, fibrofatty, fatty, and calcified)	Compare percentages of type of plaque (fibrous, fibrofatty, fatty, and calcified) within the total plaque burden on cardiac CT images as detected by quantitative software between the two assessments	baseline (pre-treatment) and 18 months after of treatment

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: Amgen
• Investigators: Principal Investigator: Daniel S. Berman, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): January 28, 2023
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Calcium Metabolism Disorders; Cardiovascular Diseases; Hyperlipidemias; Calcinosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Serine Proteinase Inhibitors; Cariostatic Agents; Listerine; Fluorides; Sodium Fluoride; Evolocumab; PCSK9 Inhibitors
• Other Study ID Numbers: 54274

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes