An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia

An 8-Week Open-Label, Sequential, Repeated Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia Followed by an Extension Phase

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.

For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks).

For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 [+1] weeks, open-label dose finding treatment period: 12 weeks).

Optional extension period: up to a maximum of 2 years for the first participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4.

For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.

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.