Assessing the Impact of Intensification of Lipid Lowering Therapy With Guidelines-based Evinacumab Administration on Coronary Plaque Volumes Measured by Coronary Computed Tomography Angiography (CCTA) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

NCT07447648 | Recruiting DMC

• 1 other identifier: EVOLVE-HoFH
• Study Type: observational
• Target: 52
• Locations: 4 countries
• Sites: 13

Brief Summary

This observational, multicenter, retrospective and prospective study aims to evaluate the impact of intensified lipid-lowering therapy including Evinacumab on coronary atherosclerotic plaque burden in patients with Homozygous Familial Hypercholesterolemia (HoFH). HoFH is a rare genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels from early life and a markedly increased risk of premature atherosclerotic cardiovascular disease. Despite combination lipid-lowering therapy, many patients do not achieve recommended LDL-C targets and remain at high cardiovascular risk. Evinacumab, a monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3), has demonstrated significant LDL-C reduction in clinical trials. However, real-world evidence on its impact on coronary plaque progression is limited. The study will compare HoFH patients receiving intensified lipid-lowering therapy including Evinacumab with patients receiving conventional lipid-lowering therapy without Evinacumab. Coronary plaque burden and phenotype will be assessed using coronary computed tomography angiography (CCTA) performed as part of routine clinical practice. Approximately 52 patients will be enrolled across European centers. The primary objective is to evaluate changes in non-calcified coronary plaque volume between baseline and 18-24 months' follow-up. Secondary objectives include evaluation of total plaque burden, high-risk plaque characteristics, and LDL-C reduction. Exploratory analyses will assess patient-reported outcomes, pericoronary adipose tissue characteristics, and supravalvular atherosclerosis. All data are collected from routine clinical care. No additional procedures are mandated by the protocol. This study aims to generate real-world imaging evidence on the effect of intensified lipid-lowering therapy including Evinacumab on coronary atherosclerosis in HoFH.

Conditions

Coronary Computed Tomography Angiography; Homozygous Familial Hypercholesterolemia (HoFH)

Keywords

Evinacumab; Homozygous Familial Hypercholesterolemia; Cardiovascular Disease; LDL Cholesterol; Lipid-Lowering Therapy; Lipid Metabolism Disorders; Atherosclerosis; Rare Genetic Disorders; Coronary Computed Tomography Angiography

Outcome Measures

Primary Outcomes (1)

• Stabilization or regression of atherosclerotic coronary plaques as measured by CCTA in Evinacumab patients vs conventional ones

  This measure will compare the change in percent of non-calcified coronary plaque volume (NCPV) between baseline and follow-up, as assessed by CCTA, in HoFH patients receiving intensified lipid lowering therapy including Evinacumab versus those managed with conventional lipid-lowering therapy under routine clinical care.

  Baseline, 6 months, 12 months, 18-24 months

Secondary Outcomes (9)

• Change in absolute NCPV, TPV and CPV

  Baseline, 6 months, 12 months, 18-24 months

• Change in percent NCPV, PAV and CPV

  Baseline, 6 months, 12 months, 18-24 months

• Change in absolute and percent NCPV, TPV, CPV and PAV

  Baseline, 6 months, 12 months, 18-24 months

• Low attenuation non-calcified plaque volume

  Baseline, 6 months, 12 months, 18-24 months

• Change in segment involvement score

  Baseline, 6 months, 12 months, 18-24 months

Other Outcomes (6)

• Changes in patient reported outcomes (SAQ-7)

  Baseline, 6 months, 12 months, 18-24 months

• Change in PCAT attenuation in RCA

  Baseline, 6 months, 12 months, 18-24 months

• Characterization of supravalvular atherosclerosis

  Baseline, 6 months, 12 months, 18-24 months

Study Arms (2)

Intensified treatment cohort with Evinacumab

Male and Female HoFH patients aged ≥12 (exception for Italy and France ≥18 years) who initiated commercially available Evinacumab (at the approved dosage and administration) as add-on lipid-lowering treatment (with statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before Evinacumab initiation, in the routine clinical care. The study will evaluate, in a real-world setting with a retrospective and prospective observational design, whether intensification of lipid-lowering therapy with Evinacumab is associated with stabilization or regression of coronary atherosclerotic plaques, as assessed by CCTA, compared with the conventional treatment cohort

Conventional treatment cohort

Male and Female HoFH patients aged ≥12 (exception for Italy and France ≥18 years) on standard lipid-lowering therapy (with statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before the baseline CCTA from: 1. countries where Evinacumab will not be commercially available within the next 18 months; 2. participating countries who have the explicit wish not to receive treatment with Evinacumab.

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Intensified treatment group: Male and Female HoFH patients aged ≥12 (exception for Italy and France ≥18 years) who initiated commercially available Evinacumab (at the approved dosage and administration) as add-on lipid-lowering treatment at stable dose for at least 30 days before Evinacumab initiation, in the routine clinical care. Conventional treatment group: Male and Female HoFH patients aged ≥12 (exception for Italy and France ≥18 years) on standard lipid-lowering therapy at stable dose for at least 30 days before the baseline CCTA from: 1. countries where Evinacumab will not be commercially available within the next 18 months; 2. participating countries who have the explicit wish not to receive treatment with Evinacumab.

You may qualify if:

• Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
• Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
• Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
• Patients who initiated Evinacumab (at the approved dosage and administration) within 24 months before enrolment as add-on to lipid-lowering treatment (with statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before Evinacumab initiation, as per routine clinical care and no change in dosing is anticipated.
• Availability of a baseline CCTA performed at least 6 months prior or 1 month after Evinacumab initiation and a follow-up CCTA performed 18-24 months after Evinacumab initiation.
• LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.
• Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
• Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
• Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
• Patients with HoFH on standard lipid-lowering therapy (statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before a baseline CCTA and with a follow-up CCTA after 18-24 months from the baseline one.
• Required lipid lowering therapies: statin, ezetimibe and PCSK9 directed therapy (unless discontinuation due to \<15% LDL-cholesterol reduction).
• Optional additional lipid-lowering therapies:
• Lipoprotein apheresis, at stable intervals for at least 3 months.
• Lomitapide, at stable dose for at least 3 months.
• LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.

You may not qualify if:

• Patients participating in a clinical trial with an investigational drug within the last 6 months.
• Patients treated outside of Evinacumab approved indication.
• Inability to access adequate retrospective clinical data from medical records.
• Inability or unwillingness to provide informed consent/assent or refusal to participate.
• Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
• Pregnancy at the time of the LLT administration.
• Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.
• Participation in any interventional clinical trial involving investigational drugs within the last 6 months.
• Inability to access adequate retrospective clinical data from medical records.
• Inability or unwillingness to provide informed consent/assent or refusal to participate.
• Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
• Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.
• Pregnancy at the time of the LLT administration.

Sponsors & Collaborators

• Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi): lead
• Ultragenyx Pharmaceutical Inc: collaborator
• CMV-Stat S.r.l.: collaborator
• Clinical Trial Consulting s.s.: collaborator

Study Sites (13)

Unité de Lipidologie et Prévention Cardiovasculaire, Centre de Compétence Dyslipidémies Rares (CEDRA), Service de Nutrition, Hôpital Pitié-Salpétriêre

Paris, France

NOT YET RECRUITING

Dipartimento Scienze-Cardiovascolari, AO "Sant'Anna e San Sebastiano" di Caserta

Caserta, Italy

RECRUITING

U.O.C. di Medicina Interna, P.O. Nesima, ARNAS Garibaldi

Catania, Italy

NOT YET RECRUITING

Nefrologia e Emodialisi, Centro Aterosclerosi e Dislipidemie, Ospedale Bassini, ASST Nord Milano

Cinisello Balsamo, Italy

RECRUITING

Malattie Aterotrombotiche, Azienda Ospedaliero Universitaria Careggi

Florence, Italy

RECRUITING

DAI di Medicina Clinica, Centro di Riferimento Regionale di Lipidologia e Dislipidemie, AOU Federico II di Napoli

Naples, Italy

RECRUITING

UOC Clinica Medica I, AOU di Padova

Padova, Italy

NOT YET RECRUITING

U.O. Astanteria/MCAU AOU, Policlinico "Paolo Giaccone" di Palermo

Palermo, Italy

RECRUITING

Centro per le Malattie Rare del Metabolismo dei Lipidi, Unità di Medicina Interna e Malattie Metaboliche, Dipartimento di Medicina Traslazionale e di Precisione Sapienza, Università di Roma

Roma, Italy

RECRUITING

Medicina Interna, Ospedale Molinette, AOU Città della Salute e della Scienza

Torino, Italy

NOT YET RECRUITING

Amsterdam University Medical Center, Amsterdam UMC, locatie AMC

Amsterdam, Netherlands

RECRUITING

Erasmus University Medical Center, Dr. Molewaterplein 40

Rotterdam, Netherlands

NOT YET RECRUITING

Ege University,Director of Lipid and Prevention Clinic, Department of Cardiology

Bornova, Turkey (Türkiye)

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected and retained for lipid profile analysis, liver function tests (ALT and AST) and other biochemical assessments related to the study objectives as for example white blood cell count, differential white blood cell count, C-reactive protein, creatinine and creatine kinase. CCTA images will be collected and retained for analysis related to the study objectives.

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia; Cardiovascular Diseases; Lipid Metabolism Disorders; Atherosclerosis

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: March 3, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 1, 2029
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1); NL (2); FR (1); IT (9)