Dyslipidemia, Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Conditions
Keywords
Lomitapide, Hypercholesterolemia, Cardiovascular Disease, LDL Cholesterol, Lipid-Lowering Therapy, Lipid Metabolism Disorders, Atherosclerosis, Rare Genetic Disorders
Brief summary
This observational, multicenter, retrospective and prospective study aims to evaluate the effect of lomitapide treatment on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH). HoFH is a rare genetic disorder characterized by extremely high levels of LDL cholesterol (LDL-C), leading to an increased risk of early cardiovascular diseases. Lomitapide is an approved medication that lowers LDL-C levels by inhibiting microsomal triglyceride transfer protein (MTP). The study will collect data from patients who have been treated with lomitapide for at least 12 months and will compare the incidence of MACE during the first three years of treatment with the three years before treatment initiation. The study includes data collection from multiple lipid centers across Europe. The primary objective is to assess the impact of lomitapide on MACE, while secondary objectives include evaluating changes in lipid profiles, liver function tests, and lipid-lowering treatments.
Detailed description
This is a multicenter, international, long-term observational study investigating the real-world impact of lomitapide on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH). Study Design: Observational, open-label, retrospective and prospective study Data will be collected from 30 lipid centers across Europe Patients will serve as their own control, with comparisons between pre-treatment (3 years before lomitapide) and post-treatment (first 3 years of lomitapide therapy) periods Study Population: Approximately 72 adult patients (≥18 years) diagnosed with HoFH Patients must have received lomitapide for at least 12 months Availability of 3 years of pre-treatment clinical records Objectives: Primary Objective: Evaluate the incidence of MACE before and after lomitapide treatment Secondary Objectives: Assess changes in LDL-C, total cholesterol, liver function tests (ALT, AST, GGT), and lipid-lowering therapy usage (e.g., discontinuation of LDL apheresis, addition of PCSK9 inhibitors) Endpoints: Primary Endpoint: Change in MACE incidence over the 3-year treatment period Secondary Endpoints: Changes in lipid levels, liver safety markers, and adherence to treatment protocols Safety Considerations: The study follows real-world clinical practice, with monitoring of adverse events, including liver-related safety concerns associated with lomitapide Data will be collected in an electronic Case Report Form (eCRF) and analyzed following Good Clinical Practice (GCP) guidelines This study aims to generate real-world evidence on the cardiovascular impact of lomitapide in HoFH patients, addressing an unmet clinical need for data on long-term outcomes.
Interventions
None listed
Sponsors
Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)
Amryt Pharmaceuticals DAC
Clinical Trial Consulting
CMV-Stat S.r.l.
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (age ≥18 years) * Clinical or genetic diagnosis of HoFH * Treated with lomitapide at any dosage * On treatment with lomitapide for at least 12 months at the time of enrollment * Availability of 3 years of medical records prior to lomitapide treatment to confirm MACE * Giving written informed consent
Exclusion criteria
* Patients who were prescribed lomitapide outside of the marketing authorization or in contraindicated patients * Patients receiving lomitapide in clinical trials * Patients receiving an investigational agent, defined as any drug or biologic agent other than lomitapide that has not received Market Authorization in the country of participation, at the time of enrolment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Major Adverse Cardiovascular Events (MACE) Before and After Lomitapide Treatment | 3 years before treatment vs. 3 years during treatment | This measure will assess the incidence of MACE (including myocardial infarction, stroke, cardiovascular death, and hospitalization due to unstable angina) during the first three years of lomitapide treatment compared to the three years prior to treatment initiation. Unit of Measure: Number of events per 100 patient-years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in LDL-Cholesterol Levels | Baseline, 1 year, 2 years, 3 years | This measure will evaluate changes in LDL-C levels. Unit of Measure: mg/dL. |
| Change in Total Cholesterol, Triglycerides, and HDL-Cholesterol | Baseline, 1 year, 2 years, 3 years | Assess changes in total cholesterol, triglycerides, and HDL-C at 1, 2, and 3 years after lomitapide treatment initiation. Unit of Measure: mg/dL. |
| Change in Triglyceride Levels | Baseline, 1 year, 2 years, 3 years. | This measure will evaluate changes in triglyceride levels. Unit of Measure: mg/dL. |
| Change in HDL-Cholesterol Levels | Baseline, 1 year, 2 years, 3 years | This measure will evaluate changes in HDL-C levels. Unit of Measure: mg/dL. |
| Liver Safety Profile - ALT Levels | Baseline, 1 year, 2 years, 3 years. | This measure will evaluate changes in alanine aminotransferase (ALT) levels. Unit of Measure: U/L. |
| Liver Safety Profile - AST Levels | Baseline, 1 year, 2 years, 3 years. | This measure will evaluate changes in aspartate aminotransferase (AST) levels. Unit of Measure: U/L. |
| Liver Safety Profile - GGT Levels | Baseline, 1 year, 2 years, 3 years. | This measure will evaluate changes in gamma-glutamyl transferase (GGT) levels. Unit of Measure: U/L. |
| Lipid-Lowering Therapy Modifications | Baseline, 1 year, 2 years, 3 years. | This measure will track changes in lipid-lowering therapies, for example the discontinuation of LDL apheresis or the introduction of evinacumab, as described in the study protocol. Unit of Measure: Number of patients with therapy modifications. |
Countries
France, Greece, Italy, Netherlands, United Kingdom
Outcome results
None listed