An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia
Condition: Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia
Intervention: Alirocumab SAR236553 (REGN727); Atorvastatin; Simvastatin; Fluvastatin; Pravastatin; Lovastatin; Rosuvastatin; Ezetimibe; Cholestyramine; Nicotinic acid; Fenofibrate; Omega-3 fatty acids
Intervention description: Pharmaceutical form: solution for injection in pre-filled syringe,
Route of administration: subcutaneous (SC); Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: capsule,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: oral suspension,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: tablet,
Route of administration: oral; Pharmaceutical form: capsule,
Route of administration: oral
Intervention MeSH terms: Nicotinic Acids; Niacin; Niacinamide; Atorvastatin; Rosuvastatin Calcium; Simvastatin; Ezetimibe; Pravastatin; Alirocumab; Lovastatin; Cholestyramine Resin; Fenofibrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 8 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Pediatrics, Homozygous Familial Hypercholesterolemia, Alirocumab, PCSK9 inhibitor, Low-density Lipoprotein Cholesterol (LDL-C)

Summary:

      Primary Objective:

      To evaluate the efficacy of alirocumab (75 or 150 milligrams [mg] depending on body weight
      [BW]), administered every 2 weeks (Q2W), on low-density lipoprotein cholesterol (LDL-C)
      levels at Week 12 of treatment in children and adolescents with homozygous familial
      hypercholesterolemia (hoFH) of 8 to 17 years of age on top of background treatments.

      Secondary Objectives:

        -  To evaluate the efficacy of alirocumab after 24 and 48 weeks of treatment on LDL-C
           levels.

        -  To evaluate the effects of alirocumab on other lipid parameters (eg, apolipoprotein B
           [Apo B], non-high density lipoprotein cholesterol [non-HDL-C], total cholesterol
           [Total-C], high density lipoprotein cholesterol [HDL-C], lipoprotein a [Lp (a)],
           triglycerides [TG], apolipoprotein A-1 [Apo A-1] levels) after 12, 24, and 48 weeks of
           treatment.

        -  To evaluate the safety and tolerability of alirocumab up to 48 weeks of treatment.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants genetically diagnosed with hoFH.

          -  Participants treated with optimal dose of statin +/- other lipid modifying therapies
             (LMTs), or non-statin LMTs if statin-intolerant at stable dose(s) for at least 4
             weeks.

          -  A signed informed consent indicating parental permission with or without participants
             assent.

          -  For participants on apheresis, currently undergoing stable LDL apheresis therapy prior
             to the screening visit (Week -2) and had initiated apheresis treatment for at least 6
             months.

        Exclusion criteria:

          -  Participants with LDL-C <130 milligram per deciliter [mg/dL] (3.37 millimoles per
             liter [mmol/L]) obtained during the screening period after the participant had been on
             stable apheresis procedure or LMT (i.e., stable optimal dose of statin ± other stable
             LMTs, or stable non statin LMTs in statin-intolerant participants) treatment for at
             least 4 weeks.

          -  Participants with BW <25 kg.

          -  Participants aged 8 to 9 years not at Tanner Stage 1 and participants aged of 10 to 17
             years not at least at Tanner Stage 2 in their development.

          -  Participants with uncontrolled Type 1 or 2 diabetes mellitus.

          -  Participants with known uncontrolled thyroid disease.

          -  Participants with uncontrolled hypertension.

          -  Participants who will receive statin de novo during the run-in period.

          -  Fasting triglycerides greater than (>) 350 mg/dL (3.95 mmol/L) at the screening visit.

          -  Severe renal impairment (i.e., estimated glomerular filtration rate <30 milliliter per
             minute/1.73 meter square) at the screening visit.

          -  Alanine aminotransferase or aspartate aminotransferase >2 * upper limit of normal
             (ULN) at the screening visit.

          -  Creatine phosphokinase >3 * ULN at the screening visit.

        The above information was not intended to contain all considerations relevant to a
        participants potential participation in a clinical trial.