An observational study in Homozygous Familial Hypercholesterolemia (HoFH) and Coronary Computed Tomography Angiography, sponsored by Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi). Recruiting at 13 sites in 4 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-08-21.
Sponsored by Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi) · Observational
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.
This is a multicenter, international, non-profit, observational study with retrospective and prospective data collection evaluating the real-world impact of intensified lipid-lowering therapy including Evinacumab on coronary atherosclerosis in patients with Homozygous Familial Hypercholesterolemia (HoFH).
Background and Rationale
HoFH is characterized by markedly elevated LDL-C levels due to impaired LDL receptor function, leading to accelerated and diffuse atherosclerosis and early cardiovascular morbidity and mortality. Despite aggressive combination therapy (statins, ezetimibe, PCSK9 inhibitors, lomitapide, and lipoprotein apheresis), most patients fail to reach LDL-C targets.
Evinacumab is a fully human monoclonal antibody directed against ANGPTL3 and lowers LDL-C independently of LDL receptor activity. Clinical trials have demonstrated approximately 50% LDL-C reduction in HoFH patients. However, the effect of Evinacumab on coronary plaque burden and phenotype in real-world clinical practice has not been systematically evaluated.
Coronary computed tomography angiography (CCTA) allows non-invasive quantification of total plaque burden, differentiation of calcified and non-calcified plaque, and identification of high-risk plaque features. Imaging-based plaque assessment represents a validated surrogate of atherosclerosis progression and cardiovascular risk.
Study Design
This is a non-interventional, observational study conducted in approximately 25 European centers. The study includes both retrospective data (up to 30 months prior to enrollment) and prospective follow-up (up to 24 months).
Patients are allocated to cohorts based exclusively on routine clinical care decisions:
No therapeutic interventions are mandated or modified by the study protocol.
Study Population
Approximately 52 patients are expected to be enrolled (approximately 35 in the intensified treatment group and 17 in the conventional treatment group). Eligible patients must have a clinical or genetic diagnosis of HoFH and available baseline and follow-up CCTA scans performed according to routine clinical practice.
Objectives
Primary Objective:
To assess whether intensification of lipid-lowering therapy including Evinacumab is associated with stabilization or regression of coronary atherosclerotic plaques compared with conventional therapy, as measured by change in percent non-calcified plaque volume (NCPV) between baseline and follow-up CCTA.
Secondary Objectives:
Exploratory Objectives:
Imaging Analysis
CCTA scans performed in routine care will be analyzed centrally using standardized, FDA-cleared artificial intelligence-based quantitative software. Blinded core laboratory analysis will ensure consistency across sites.
Statistical Considerations
The primary endpoint is the annualized change in percent NCPV from baseline to 18-24 months. Between-group comparisons will be performed using appropriate parametric or non-parametric tests. Secondary and exploratory endpoints will be analyzed descriptively and comparatively.
Safety
As a non-interventional study, safety data will be collected from routine clinical documentation. Treatment decisions remain under the responsibility of the treating physician.
Conclusion
This study will provide real-world imaging data on the effect of intensified lipid-lowering therapy including Evinacumab on coronary plaque burden and phenotype in HoFH patients. The findings may contribute to optimizing cardiovascular risk management strategies in this high-risk population.
68 studies on the registry are indexed under Homozygous Familial Hypercholesterolemia; 13 are open to participants now.
This study's planned enrollment of 52 is below the median of 167 across 14 observational studies indexed under Homozygous Familial Hypercholesterolemia.
Browse Homozygous Familial Hypercholesterolemia studies →Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi) is the lead sponsor of 5 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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:
Inclusion Criteria (intensified treatment group - Evinacumab):
Inclusion criteria (conventional treatment group - No Evinacumab)
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.
Exclusion criteria (intensified treatment group - Evinacumab)
Exclusion criteria (conventional treatment group - No Evinacumab)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in absolute NCPV, TPV and CPV
Asses changes in absolute NCPV, total plaque volume (TPV) and calcified plaque volume (CPV) from baseline to follow-up within each treatment group.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in percent NCPV, PAV and CPV
Asses changes in percent NCPV, percent atheroma volume (PAV) and percent CPV from baseline to follow-up within each treatment group.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in absolute and percent NCPV, TPV, CPV and PAV
Assess Differences in change between groups (Evinacumab vs. conventional therapy) for absolute and percent NCPV, TPV, CPV, and PAV.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Low attenuation non-calcified plaque volume
Assess low attenuation non-calcified plaque volume (ideally \<30 HU)
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in segment involvement score
Assess changes in segment involvement score
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in absolute and percent of LDL-Cholesterol levels
Assess changes in LDL-Cholesterol levels (absolute and percent) between baseline and follow-up, both within and between treatment groups.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Positive remodeling
Assess remodeling index (if positive \> 1.1)
Time frame: Baseline, 6 months, 12 months, 18-24 months
Combined features defining high-risk plaque
Assess combined features defining high-risk plaque
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in plaque phenotype conversion
Assess changes in plaque phenotype conversion (e.g. from non-calcified to calcified).
Time frame: Baseline, 6 months, 12 months, 18-24 months
Changes in patient reported outcomes (SAQ-7)
Assess symptoms related to angina pectoris using a standard questionnaire (SAQ-7) from baseline to follow-up in the intensified treatment and conventional treatment comparator group and also between the two groups. The Seattle Angina Questionnaire is used to assess the frequency and impact of chest pain, chest tightness, or angina over the previous four weeks. The questionnaire evaluates physical limitation during daily activities, frequency of angina episodes, frequency of nitroglycerin use, the extent to which symptoms limit enjoyment of life, and overall satisfaction with current symptom status. Responses are provided using Likert-type scales, with higher scores reflecting better health status and fewer symptom-related limitations.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in PCAT attenuation in RCA
Assess changes in PCAT Attenuation (Hounsfield Units) in Right Coronary Artery (RCA).
Time frame: Baseline, 6 months, 12 months, 18-24 months
Characterization of supravalvular atherosclerosis
Characterization of supravalvular atherosclerosis as assessed by available CCTA, including its presence, distribution, and potential changes over time.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Changes in patient reported outcomes (Rose Dyspnea Scale)
Assess symptoms related to dyspnea using a standard questionnaire (Rose Dyspnea Scale) from baseline to follow-up in the intensified treatment and conventional treatment comparator group and also between the two groups. The Dyspnea Score ranges from 0 to 4: a score of 0 indicates no dyspnea; 1 indicates dyspnea only when hurrying or walking up a hill; 2 indicates dyspnea when walking on level ground with people of the same age; 3 indicates dyspnea when walking at one's own pace on level ground; 4 indicates dyspnea during activities of daily living such as washing or dressing.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Changes in patient reported outcomes (PHQ-2)
Assess symptoms related to depression using a standard questionnaire (PHQ-2) from baseline to follow-up in the intensified treatment and conventional treatment comparator group and also between the two groups. Over the last two weeks, patients are asked how often they have been bothered by specific problems. The first item assesses little interest or pleasure in doing things and the second assesses feeling down, depressed, or hopeless. Each item is scored on a 4-point scale: 0 for "not at all," 1 for "several days," 2 for "more than half the days," and 3 for "nearly every day." The total score is calculated by summing the scores of the two items.
Time frame: Baseline, 6 months, 12 months, 18-24 months
Change in PCAT Attenuation in LAD
Assess changes in PCAT Attenuation (Hounsfield Units) in Left Anterior Descending Artery (LAD).
Time frame: Baseline, 6 months, 12 months, 18-24 months
Plan to share: No — The EVOLVE-HoFH study collects observational data on patients treated with Evinacumab and/or conventional lipid-lowering therapies in compliance with data protection regulations (GDPR) and Good Clinical Practice (GCP) guidelines. At this time, individual participant data (IPD) sharing is not planned to ensure confidentiality and adherence to ethical and legal requirements. However, aggregated study results will be made available through scientific publications and regulatory reports.
No publications or documents are linked to this record.
Started Apr 2026 (actual). Primary completion is estimated for Sep 2027, 17 months after the start.
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Homozygous Familial Hypercholesterolemia →
Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)