study in participants with homozygous familial hypercholesterolemia (hofh)

Conditions: Homozygous Familial Hypercholesterolemia

Summary: the primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (ldl-c) with alirocumab subcutaneous (sc) every 2 weeks (q2w) in comparison to placebo after 12 weeks of treatment. the secondary objectives of the study are: * to evaluate the effect of alirocumab q2w on other lipid parameters (ie, apolipoprotein \[apo\] a-1 and b, non-high-density lipoprotein cholesterol \[non-hdl-c\], total-cholesterol \[tc\], proportion of participants with 15%, 30%, and 50% ldl-c reductions, lp(a), hdl-c, triglycerides \[tg\]) in participants with hofh * to evaluate the safety and tolerability of alirocumab sc q2w in participants with hofh * to assess the pharmacokinetics of alirocumab sc q2w in participants with hofh * to assess the potential development of anti-drug (alirocumab) antibodies


Eligibility criteria:
note: the information listed below is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial, therefore not all inclusion/exclusion criteria are listed. key inclusion criteria 1. diagnosis of hofh by at least 1 of the following genotype or clinical criteria (all patients on ldl apheresis must be diagnosed based on genotype): 1. documented homozygous or compound heterozygous mutations in both low-density lipoprotein receptor (ldlr) alleles 2. presence of homozygous or compound heterozygous mutations in apo b, pcsk9 or ldl receptor adaptor protein 1 (ldlrap1) 3. presence of double heterozygous mutations, i.e, mutations on different genes in the ldlr, apo b or pcsk9 alleles 4. untreated tc \>500 mg/dl (12.93 mmol/l) and tg \ 250 mg/dl (6.46 mmol/l) or cutaneous or tendinous xanthoma before age 10 2. receiving a stable dose of a statin at the screening visit (documentation if statin ineffective or patient unable to tolerate statin) 3. if undergoing ldl apheresis, must have initiated ldl apheresis at least 3 months prior to screening and must have been on a stable weekly (every 7 days) or every other week (every 14 days) schedule or stable settings for at least 8 weeks key exclusion criteria: 1. documented evidence of a null mutation in both ldlr alleles 2. use of a pcsk9 inhibitor within 10 weeks from screening visit 3. background medical lipid modifying therapy (lmt) that has not been stable for at least 4 weeks (6 weeks for fibrates, 24 weeks for mipomersen, 12 weeks for maximum tolerated dose of lomitapide) before the screening visit. 4. ldl apheresis schedule/apheresis settings that have not been stable for at least 8 weeks before the screening visit or an apheresis schedule/settings that is not anticipated to be stable over the next 24 weeks. 5. use of nutraceuticals or over-the-counter (otc) therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit or between the screening and randomization visits. 6. chronic use of systemic corticosteroids, unless on a stable regimen of 10 mg daily prednisone equivalent or less for at least 6 weeks prior to randomization. note: topical, intra-articular, nasal, inhaled and ophthalmic steroid therapies are not considered as 'systemic' and are allowed 7. systolic blood pressure \>160 mmhg or diastolic blood pressure \>100 mmhg at the screening visit (1 repeat measurement is allowed). 8. ldl-c level \<70 mg/dl (1.81 mmol/l) at the screening visit 9. history of a myocardial infarction (mi), unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention , uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit.