Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
Condition: Homozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia
Intervention: Alirocumab; Placebo
Intervention description: Alirocumab SC Q2W; Matching placebo SC Q2W
Intervention MeSH terms: Alirocumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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 <300 mg/dL (3.39 mmol/L) AND Both
                  parents with history of TC >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.