An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Status and phase
Completed
Phase 3
Conditions
Hypercholesterolaemia
Treatments
Drug: Rosuvastatin
Drug: Atorvastatin
Drug: Placebo
Drug: Alirocumab SAR236553 (REGN727)
Drug: Ezetimibe
Drug: Cholestyramine
Drug: Fluvastatin
Drug: Fenofibrate
Drug: Nicotinic acid
Drug: Lovastatin
Drug: Simvastatin
Drug: Pravastatin
Drug: Omega-3 fatty acids
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
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.
Full 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).
Enrollment
153 patients
Sex
All
Ages
8 to 17 years old
Volunteers
No Healthy Volunteers
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.
Trial design
Primary purpose
Treatment
Allocation
Randomized
Interventional model
Parallel Assignment
Masking
Triple Blind
153 participants in 4 patient groups
Placebo/Alirocumab Q2W
Experimental group
Description:
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).
Treatment:
Drug: Fenofibrate
Drug: Alirocumab SAR236553 (REGN727)
Drug: Fluvastatin
Drug: Omega-3 fatty acids
Drug: Nicotinic acid
Drug: Lovastatin
Drug: Simvastatin
Drug: Pravastatin
Drug: Placebo
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Rosuvastatin
Drug: Cholestyramine
Alirocumab Q2W
Experimental group
Description:
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).
Treatment:
Drug: Fenofibrate
Drug: Alirocumab SAR236553 (REGN727)
Drug: Fluvastatin
Drug: Omega-3 fatty acids
Drug: Nicotinic acid
Drug: Lovastatin
Drug: Simvastatin
Drug: Pravastatin
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Rosuvastatin
Drug: Cholestyramine
Placebo/Alirocumab Q4W
Experimental group
Description:
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).
Treatment:
Drug: Fenofibrate
Drug: Alirocumab SAR236553 (REGN727)
Drug: Fluvastatin
Drug: Omega-3 fatty acids
Drug: Nicotinic acid
Drug: Lovastatin
Drug: Simvastatin
Drug: Pravastatin
Drug: Placebo
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Rosuvastatin
Drug: Cholestyramine
Alirocumab Q4W
Experimental group
Description:
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).
Treatment:
Drug: Fenofibrate
Drug: Alirocumab SAR236553 (REGN727)
Drug: Fluvastatin
Drug: Omega-3 fatty acids
Drug: Nicotinic acid
Drug: Lovastatin
Drug: Simvastatin
Drug: Pravastatin
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Rosuvastatin
Drug: Cholestyramine
Trial contacts and locations
43
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Data sourced from clinicaltrials.gov
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