Vanderbilt Clinical Trials

An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia

Purpose

Primary Objective: To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W) and every 4 weeks (Q4W) versus placebo after 24 weeks of double-blind (DB) treatment on low-density lipoprotein cholesterol (LDL-C) levels in participants with heterozygous familial hypercholesterolemia (heFH) 8 to 17 years of age 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. Secondary Objectives: - To evaluate the efficacy of alirocumab versus placebo on LDL-C levels. - To evaluate the effects of alirocumab versus placebo on other lipid parameters. - To evaluate the safety and tolerability of alirocumab in comparison with placebo. - To evaluate the efficacy, safety, and tolerability of alirocumab after open label treatment. - To evaluate the development of anti-alirocumab antibodies.

Condition

Hypercholesterolaemia

Eligibility

Eligible Ages: Between 8 Years and 17 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Children and adolescent male and female participants 8 to 17 years of age at the time of signed informed consent. - Participants with diagnosis of 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 except for participants who have previously participated in the DFI14223 (NCT02890992) study. - A signed informed consent indicating parental permission with or without participant assent.

Exclusion Criteria

Participant with body weight < 25 kg. - Participants aged of 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 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. - Participants with uncontrolled type 1 or type 2 diabetes mellitus. - Participants with known uncontrolled thyroid disease. - Participants with uncontrolled hypertension. - Fasting triglycerides greater than (>) 350 mg/dL (3.95 mmol/L). - Severe renal impairment (ie, estimated glomerular filtration rate <30 mL/min/1.73 m^2). - Alanine aminotransferase or aspartate aminotransferase >2*upper limit of normal (ULN). - Creatinine phosphokinase (CPK) >3*ULN. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Triple (Participant, Care Provider, Investigator)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Placebo/Alirocumab Q2W	Participants received subcutaneous (SC) injection of placebo (matched to alirocumab) based on their body weight (BW) (less than [<] 50 kilograms [kg] or greater than or equal to [>=] 50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 milligrams (mg) (for BW <50 kg) or 75 mg (for BW >=50 kg) Q2W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW <50 kg) or 75 mg to 150 mg (for BW >=50 kg) or down titrated as 75 mg to 40 mg (for BW <50 kg) or 150 mg to 75 mg (for BW >=50 kg).	Drug: Alirocumab SAR236553 (REGN727) Pharmaceutical form:solution Route of administration: subcutaneous injection Other names: Praluent Drug: Rosuvastatin Pharmaceutical form:tablet Route of administration: oral Drug: Atorvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Simvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Pravastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Lovastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Fluvastatin Pharmaceutical form:Capsule Route of administration: Oral Drug: Ezetimibe Pharmaceutical form:Tablet Route of administration: Oral Drug: Cholestyramine Pharmaceutical form:oral suspension Route of administration: oral Drug: Nicotinic acid Pharmaceutical form:Tablet Route of administration: Oral Drug: Fenofibrate Pharmaceutical form:Tablet Route of administration: Oral Drug: Omega-3 fatty acids Pharmaceutical form:capsule Route of administration: oral Drug: Placebo Pharmaceutical form:solution Route of administration: subcutaneous injection
Experimental Alirocumab Q2W	Participants received SC injection of alirocumab 40 mg (for BW <50 kg) or 75 mg (for BW >=50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level was >=110 milligrams per deciliter (mg/dL) (2.85 millimoles per liter [mmol/L]) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 mg (for BW <50 kg) or 75 mg (for BW >=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW <50 kg) or 75 mg to 150 mg (for BW >=50 kg) or down titrated as 75 mg to 40 mg (for BW <50 kg) or 150 mg to 75 mg (for BW >=50 kg).	Drug: Alirocumab SAR236553 (REGN727) Pharmaceutical form:solution Route of administration: subcutaneous injection Other names: Praluent Drug: Rosuvastatin Pharmaceutical form:tablet Route of administration: oral Drug: Atorvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Simvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Pravastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Lovastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Fluvastatin Pharmaceutical form:Capsule Route of administration: Oral Drug: Ezetimibe Pharmaceutical form:Tablet Route of administration: Oral Drug: Cholestyramine Pharmaceutical form:oral suspension Route of administration: oral Drug: Nicotinic acid Pharmaceutical form:Tablet Route of administration: Oral Drug: Fenofibrate Pharmaceutical form:Tablet Route of administration: Oral Drug: Omega-3 fatty acids Pharmaceutical form:capsule Route of administration: oral
Experimental Placebo/Alirocumab Q4W	Participants received SC injection of placebo (matched to alirocumab) based on their BW (<50 kg or >=50 kg) Q4W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) Q4W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW <50 kg) or 300 mg Q4W to 150 mg Q2W (for BW >=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW <50 kg) or 150 mg Q2W to 75 mg Q2W (for BW >=50 kg).	Drug: Alirocumab SAR236553 (REGN727) Pharmaceutical form:solution Route of administration: subcutaneous injection Other names: Praluent Drug: Rosuvastatin Pharmaceutical form:tablet Route of administration: oral Drug: Atorvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Simvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Pravastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Lovastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Fluvastatin Pharmaceutical form:Capsule Route of administration: Oral Drug: Ezetimibe Pharmaceutical form:Tablet Route of administration: Oral Drug: Cholestyramine Pharmaceutical form:oral suspension Route of administration: oral Drug: Nicotinic acid Pharmaceutical form:Tablet Route of administration: Oral Drug: Fenofibrate Pharmaceutical form:Tablet Route of administration: Oral Drug: Omega-3 fatty acids Pharmaceutical form:capsule Route of administration: oral Drug: Placebo Pharmaceutical form:solution Route of administration: subcutaneous injection
Experimental Alirocumab Q4W	Participants received SC injection of alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) Q4W for 24 weeks in DB treatment period added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level >=110 mg/dL (2.85 mmol/L) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW <50 kg) or 300 mg Q4W to 150 mg Q2W (for BW >=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW <50 kg) or 150 mg Q2W to 75 mg Q2W (for BW >=50 kg).	Drug: Alirocumab SAR236553 (REGN727) Pharmaceutical form:solution Route of administration: subcutaneous injection Other names: Praluent Drug: Rosuvastatin Pharmaceutical form:tablet Route of administration: oral Drug: Atorvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Simvastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Pravastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Lovastatin Pharmaceutical form:Tablet Route of administration: Oral Drug: Fluvastatin Pharmaceutical form:Capsule Route of administration: Oral Drug: Ezetimibe Pharmaceutical form:Tablet Route of administration: Oral Drug: Cholestyramine Pharmaceutical form:oral suspension Route of administration: oral Drug: Nicotinic acid Pharmaceutical form:Tablet Route of administration: Oral Drug: Fenofibrate Pharmaceutical form:Tablet Route of administration: Oral Drug: Omega-3 fatty acids Pharmaceutical form:capsule Route of administration: oral

More Details

Status: Completed
Sponsor: Sanofi

Study Contact

Detailed Description

The study duration was approximately up to 110 weeks (run-in period [if needed]: up to 4 weeks [+2 days], screening period: up to 2 weeks [+5 days], double-blind treatment period: 24 weeks, open label (OL) treatment period: 80 weeks).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.