Heterozygous familial hypercholesterolemia MedDRA version: 20.0 Level: LLT Classification code 10057099 Term: Heterozygous familial hypercholesterolaemia System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Praluent
Product Name: alirocumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: alirocumab
Other descriptive name: ALIROCUMAB
Concentration unit: mg/ml milligram(s)/mill
Sponsors
Fundación Hipercolesterolemia Familiar
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed informed consent before the beginning of specific trial procedures - ;ail or female patients, aged between 35 and 65 years - Patients with molecular diagnostic of Familial Hypercholesterolemia, enrolled on spanish registry SAFEHEART - Asymptomatc patients - Patients without previous history of clinical cardiovascular events (myocardial acute infarction, stroke, coronary revascularization...) - Patiens receiving optimized and stable treatment with maximum tolerated doses of statins in combination or not with other lipid-lowering drugs during at least three months, with inappropiate control, defined by cLDL>100mg/dl - Patiens with PAV > 30% on basal coronary ACT, carried out on the last three months before basal visit - Patients with indication of alirocumab 150 mg/ml treatment, according to patient's characteristics and technical data sheet Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 162 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Class >II cardiac insufficiency according to NYHA scale (New York Heart Association) - Cardiac Rhythm different to normal sinus rhythm (regular CF betwen 60-100 beat per min) - Previous history of myocardial acute infarction, peripheral arterial thrombosis, stroke or transient ischemic attack - Uncontrolled Hypertension, defined as systolic pressure value at rest >180mmHg at basal visit - Fast triglycerides >250 mg/dl at baseline - Type 1 or type 2 diabetes poorly controlled (HB1A>9%) - History of hereditary muscular disorders - Thyroid disease or thyroid hormone replacement therapy - Glomerular filtration rate 3 ULN levels at baseline) - High levels of creatinine kinase (>3 ULN at baseline) - Patients that have been treated previously with IPCSK9, CETP inhibitors, mipomersen and/or lomitapide - Statin-intolerant patients - Active cancer disease or previous history of cancer - Active clinically relevant infections or significative hematologycal, metabolic, gastrointestinal, endocrine or kidney dysfunction - Availability of coronary angioCT at baseline that does not fulfill technical requisites for being processed with QAngio CT software - Patients enrolled in clinical trials, except in case that study treatment has been discontinued more than 6 months before the beginning of the study - Pregnant or lactating women, or fertile women that are not willing to use an appropiate anticonceptive method
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of alirocumab on coronary atherosclerotic burden in terms of the change in percent atheroma volume (PAV) by means of atherosclerotic plaque quantification and virtual histology of the coronary tree based on the analysis of coronary computed tomography (CCTA) on asymptomatic FH patients receiving optimized and stable treatment with maximum tolerated doses of statins in combination or not with other lipid-lowering drugs.;Secondary Objective: - To evaluate the effect of alirocumab on the change of the normalized atheroma total volume (ATV) - To determine the percentage of patients that showed plaque regression - To evaluate the effect of alirocumab on the architecture and composition of the coronary wall - To evaluate the prevalence of basal aortic valve calcification and progression of calcification along the study - To evaluate the changes on lipid profile and Lp(a) levels along the study - To evaluate the security profile of alirocumab on daily practice - To evaluate the incidence and types of cardiovascular events during alirocumab treatment;Primary end point(s): Change in percent of atheroma volume (PAV) of the coronary tree between baseline (before the initiation of alirocumab) and 18 months after the beginning of alirocumab, based on angio CT images, analyzed with QAngio TC software;Timepoint(s) of evaluation of this end point: Baselline and 18 months after the beginning of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change on normalized VTA, based on ACT images at baseline and at 18 months after the beginning of alirocumab - Percentage of patients presenting atherosclerotic plaque regression 18 months after the beginning of alirocumab, based on percentage of patients showing PAV reduction or any VTA reduction from baseline - Changes in composition and architecture of atherosclerotic plaque, based on volume and percentage of fibrotic plaque, fibrofatty plaque, necrotic plaque and calcified plaque, form baseline to 18 months - Percentage of patients with aortic valve calcification and changes on calcium score, based on cuantitative measure of calcium in the aortic valve using Agatson method, based on coronary CT images without contrast administration, form baseline to 18 months - Change on cLDL and Lp(a) levels from baseline to 18 months after the beginning of alirocumab treatment - Safety profile of alirocumab, based on the development of adverse events in patients form baseline to final visit, including anomalous laboratory values, anomalies on examination or clinical AE - Incidence and type of cardiovascular events which have taken place during alirocumab treatmen, including death for ischemic cardiopathy, myocardial infarct, stroke, hospitalization for unstable angina or unplanned revascularization;Timepoint(s) of evaluation of this end point: Baseline, 3, 12 and 18 months | — |
Countries
Spain
Contacts
Public ContactDynamic Science
Dynamic Science
Outcome results
None listed