A Trial Assessing the Effectiveness of Evolocumab in Reducing the Plaque Burden in Participants With Subclinical Atheroma

NCT07803679 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 20250101
• Study Type: interventional
• Target: 308
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main aim of this trial is to demonstrate that Evolocumab plus routine lipid management is superior to routine lipid management alone in modifying plaque (non-calcified) volume as measured by Artificial Intelligence-enabled Quantitative Coronary Plaque Analysis (AI-QCPA) from Coronary Computed Tomography Angiography (CCTA).

Conditions

Coronary Artery Disease; Hypercholesterolemia; Atheroma; Atherosclerotic Plaque

Keywords

Pragmatic trial; Open-label; Coronary Computed Tomography Angiography (CCTA); AI-enabled Quantitative Coronary Plaque Analysis (AI-QCPA); Evolocumab; Routine lipid management; Stable coronary artery disease (CAD); Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitor; Non-calcified plaque (NCP)

Outcome Measures

Primary Outcomes (1)

• Change in Non-Calcified Plaque (NCP) Volume from Baseline to Week 72

  From Baseline to Week 72

Secondary Outcomes (5)

• Change From Baseline in Low Attenuation Plaque Volume

  From Baseline to Week 72

• Change From Baseline in Total Plaque Volume

  From Baseline to Week 72

• Change From Baseline in Calcified Plaque Volume

  From Baseline to Week 72

• Change From Baseline in Lumen Volume

  From Baseline to Week 72

• Change From Baseline in Lesion-specific and nadir Coronary Computed Tomography Angiography (CCTA) derived Fractional Flow Reserve (FFRct)

  From Baseline to Week 72

Study Arms (2)

Evolocumab and Routine Lipid Management

EXPERIMENTAL

Participants will receive Evolocumab via Autoinjector (AI) every 2 weeks (Q2W) plus routine lipid management.

Drug: Evolocumab; Drug: Routine Lipid Management; Device: Autoinjector

Routine Lipid Management

ACTIVE COMPARATOR

Participants will receive routine lipid management per standard of care (SoC).

Drug: Routine Lipid Management

Interventions

Evolocumab DRUG

Evolocumab will be provided as a single-dose, prefilled AI pen for fixed dose subcutaneous (SC) injection.

Also known as: AMG 145, Repatha

Evolocumab and Routine Lipid Management

Routine Lipid Management DRUG

Routine lipid management therapies will be administered at the discretion of the investigator per SoC.

Evolocumab and Routine Lipid Management; Routine Lipid Management

Autoinjector DEVICE

AI for SC injection of Evolocumab

Evolocumab and Routine Lipid Management

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At screening, one of the two following conditions must be met: Evidence of established CAD as demonstrated by: Prior non-invasive imaging modality that demonstrates at least one major epicardial vessel with mild-to-moderate obstruction (Coronary Artery Disease Reporting and Data System (CAD-RADS) 1-3) OR Presence of an abnormal coronary artery calcium (CAC) score \> 50 OR Positive stress test indicative of suspected CAD OR Presumed CAD as determined by presence of at least one of the following conditions: Known history of diabetes mellitus (DM; type 1 or 2) with at least one of the following: DM requiring insulin therapy OR DM disease onset ≥ 5 years ago OR DM with evidence of end-organ damage such as diabetic retinopathy, neuropathy, or nephropathy OR Known history of peripheral artery disease due to atherosclerosis or carotid artery atheroma.
• Low-density Lipoprotein cholesterol (LDL-C) of at least 70 milligrams per deciliter (mg/dL).
• Patients with Intermediate pre-test probability of obstructive coronary artery lesions.
• Minimal total plaque volume (TPV) of 100 cubic millimeters (mm\^3) measured during baseline AI-QCPA.
• Must be on stable lipid-lowering therapy for at least 6 weeks, with no planned changes and no plans to initiate Proprotein Convertase Subtilisin/Kexin type 9 ( PCSK9) inhibition.

You may not qualify if:

• Lifetime history of myocardial infarction (MI), ischemic stroke, or coronary revascularization.
• Symptomatic coronary artery disease or stable chronic coronary artery disease that, in the opinion of the investigator, meets criteria for urgent or elective revascularization procedures (coronary artery bypass grafting or percutaneous coronary intervention).
• Planned cardiac surgery, arterial revascularization, or planned major non-cardiac surgery during the study period.
• Contraindication to performing serial CCTA imaging such as: Severe renal insufficiency (estimated Glomerular Filtration Rate (eGFR) \< 30 milliliters per minute per 1.73 square meters (30 mL/min/1.73 m\^2) History of hypersensitivity to iodinated contrast Body weight and/or body circumference that prevent safe and successful Computed Tomography (CT) imaging, in the opinion of the investigator; Other patient-related factors that may interfere with diagnostic quality of CCTA images including: Atrial fibrillation Heart rate \>60-70 beats per minute; Tachycardia or significant arrhythmia that cannot be adequately controlled with medications to allow CCTA Irregular rhythm (including Premature Ventricular Contraction (PVCs)); Inability to sustain a breath hold for at least five seconds.
• Prior history of PCSK9 inhibitor treatment within the past 12 months or known lifetime discontinuation of prior PCSK9 inhibitor due to adverse reaction, lack of tolerability, or lack of treatment response.
• History or evidence of any other clinically significant disorder, condition (including incidental CCTA findings), or disease that, in the opinion of the investigator, would pose a risk to participant safety.
• CCTA showing any of the following: Total occlusion OR Lesion-specific FFRct value ≤ 0.80 OR Diameter stenosis of the left main coronary artery \>50 % OR Diameter stenosis of all three major coronary arteries \>50%.
• CCTA not meeting established imaging criteria after two attempts during the baseline CCTA visit as assessed by the central imaging laboratory.

Sponsors & Collaborators

• Amgen: lead

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Coronary Artery Disease; Hypercholesterolemia; Plaque, Atherosclerotic; Hypercholesterolemia, Autosomal Dominant, 3

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Central Study Contacts

Amgen Call Center

CONTACT

866-572-6436; medinfo@amgen.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open label with blinded primary endpoint assessment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 4, 2026
• Study Start (Estimated): January 31, 2027
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.