JAMA Pediatrics | Original Investigation # Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial Raul D. Santos, MD, PhD; Albert Wiegman, MD, PhD; Sonia Caprio, MD; Bertrand Cariou, MD, PhD; Maurizio Averna, MD; Yann Poulouin, MSc; Michel Scemama, MD; Garen Manvelian, MD; Genevieve Garon, MBA; Stephen Daniels, MD Supplemental content IMPORTANCE Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on statins alone and require adjunct lipid-lowering therapy (LLT); the use of alirocumab in pediatric patients requires evaluation. OBJECTIVE To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH. DESIGN, SETTING, AND PARTICIPANTS This was a phase 3, randomized clinical trial conducted between May 2018 and August 2022 at 43 centers in 24 countries. Pediatric patients aged 8 to 17 years with HeFH, LDL-C 130 mg/dL or greater, and receiving statins or other LLTs were included. Following consecutive enrollment into dosing cohorts, 25 of 99 patients screened for dosing every 2 weeks (Q2W) failed screening; 25 of 104 patients screened for dosing every 4 weeks (Q4W) failed screening. A total of 70 of 74 Q2W patients (95%) and 75 of 79 Q4W patients (95%) completed the double-blind period. INTERVENTIONS Patients were randomized 2:1 to subcutaneous alirocumab or placebo and Q2W or Q4W. Dosage was based on weight (40 mg for Q2W or 150 mg for Q4W if <50 kg; 75 mg for Q2W or 300 mg for Q4W if ≥50 kg) and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. After the 24-week double-blind period, patients could receive alirocumab in an 80-week open-label period. MAIN OUTCOMES AND MEASURES The primary end point was percent change in LDL-C from baseline to week 24 in each cohort. RESULTS Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9JAMA Pediatrics | Original Investigation # Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial Raul D. Santos, MD, PhD; Albert Wiegman, MD, PhD; Sonia Caprio, MD; Bertrand Cariou, MD, PhD; Maurizio Averna, MD; Yann Poulouin, MSc; Michel Scemama, MD; Garen Manvelian, MD; Genevieve Garon, MBA; Stephen Daniels, MD Supplemental content IMPORTANCE Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on statins alone and require adjunct lipid-lowering therapy (LLT); the use of alirocumab in pediatric patients requires evaluation. OBJECTIVE To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH. DESIGN, SETTING, AND PARTICIPANTS This was a phase 3, randomized clinical trial conducted between May 2018 and August 2022 at 43 centers in 24 countries. Pediatric patients aged 8 to 17 years with HeFH, LDL-C 130 mg/dL or greater, and receiving statins or other LLTs were included. Following consecutive enrollment into dosing cohorts, 25 of 99 patients screened for dosing every 2 weeks (Q2W) failed screening; 25 of 104 patients screened for dosing every 4 weeks (Q4W) failed screening. A total of 70 of 74 Q2W patients (95%) and 75 of 79 Q4W patients (95%) completed the double-blind period. INTERVENTIONS Patients were randomized 2:1 to subcutaneous alirocumab or placebo and Q2W or Q4W. Dosage was based on weight (40 mg for Q2W or 150 mg for Q4W if <50 kg; 75 mg for Q2W or 300 mg for Q4W if ≥50 kg) and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. After the 24-week double-blind period, patients could receive alirocumab in an 80-week open-label period. MAIN OUTCOMES AND MEASURES The primary end point was percent change in LDL-C from baseline to week 24 in each cohort. RESULTS Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9