An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Condition: Hypercholesterolaemia
MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia
Intervention: alirocumab SAR236553 (REGN727); statins; ezetimibe; cholestyramine; fenofibrate; omega-3 fatty acids; nicotinic acid
Intervention description: Pharmaceutical form: solution Route of administration: subcutaneous injection; 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: tablet Route of administration: oral; Pharmaceutical form: tablet Route of administration: oral
Intervention MeSH terms: Nicotinic Acids; Niacin; Niacinamide; Ezetimibe; Alirocumab; Cholestyramine Resin; Fenofibrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 8 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels
      after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants
      aged of 8 to 17 years, with LDL-C >=130 milligrams per deciliter (mg/dL) (3.37 millimoles per
      litre [mmol/L]) on optimal stable daily dose of statin therapy +/- other lipid modifying
      therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at
      least 4 weeks prior to the screening period.

      Secondary Objective:

        -  To evaluate the safety and tolerability of alirocumab.

        -  To evaluate the pharmacokinetics profile of alirocumab.

        -  To evaluate the effects of alirocumab on other lipid parameters.
    

Eligibility criteria:

        Inclusion criteria :

          -  Children and adolescent male and female participants aged of 8 to 17 years at the time
             of signed informed consent. For Russia only: Male and female participants aged >=12
             and <=17 years at the time of signed informed consent.

          -  Participants with diagnosis of heterozygous familial hypercholesterolemia (heFH)
             through genotyping or clinical criteria.

          -  Participants treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s)
             if statin intolerant at stable dose for at least 4 weeks prior to screening lipid
             sampling.

          -  Participants with calculated LDL-C greater than or equal to 130 mg/dL (>=3.37 mmol/L)
             at the screening visit.

          -  Participants with body weight greater than or equal to 25 kg.

          -  Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged of 10
             to 17 years to be at least at Tanner stage 2 in their development.

          -  A signed informed consent indicating parental permission with or without participant
             assent.

        Exclusion criteria:

          -  Participant with secondary hyperlipidemia.

          -  Diagnosis of homozygous familial hypercholesterolemia.

          -  Participant who had received lipid apheresis treatment within 2 months prior to the
             screening period, or has plans to receive it during the study.

          -  Known history of type 1 or type 2 diabetes mellitus.

          -  Known history of thyroid disease.

          -  Known history of hypertension.

          -  Fasting triglycerides >350 mg/dL (3.95 mmol/L).

          -  Severe renal impairment (i.e., estimated glomerular filtration rate [eGFR] <30
             mL/min/1.73 m^2).

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of
             normal (ULN).

          -  Creatinine phosphokinase (CPK) >3 x ULN.

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.