Homozygous Familial Hypercholesterolemia (HoFH)

This is a single-arm, open-label, multicenter, ascending dose Phase 1 trial that will enroll participants 18 to 75 years of age with dyslipidemias that are refractory to available treatments.

EDP167 is a double-stranded small interfering RNA (siRNA) drug targeting angiopoietin-like 3 protein (ANGPTL3), which may bring benefits for patients with dyslipidemia conditions. This is a dose exploration study in Homozygous Familial Hypercholesterolaemia (HoFH) patients to evaluate the efficacy and safety and pharmacokinetics (PK)/pharmacodynamics (PD) profiles of multiple EDP167 injections.

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.

The goal of this clinical trial is to identify different types of Familial Hypercholesterolemia (FH) in infants and newborns. Participants will: * undergo a cheek swab for genetic testing (parents only) * have 5 blood samples collected Participants can expect to be in the trial for 2 years.