PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The primary end point was percent change in LDL-C from baseline to week 24 in each cohort.
UNASSIGNED: Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9%] female), alirocumab showed statistically significant reductions in LDL-C vs placebo in both cohorts at week 24. Least squares mean difference in percentage change from baseline was -43.3% (97.5% CI, -56.0 to -30.7; P < .001) Q2W and -33.8% (97.5% CI, -46.4 to -21.2; P < .001) Q4W. Hierarchical analysis of secondary efficacy end points demonstrated significant improvements in other lipid parameters at weeks 12 and 24 with alirocumab. Two patients receiving alirocumab Q4W experienced adverse events leading to discontinuation. No significant difference in adverse event incidence was observed between treatment groups. Open-label period findings were consistent with the double-blind period.
UNASSIGNED: The findings in this study indicate that alirocumab Q2W or Q4W significantly may be useful for reducing LDL-C and other lipid parameters and be well tolerated in pediatric patients with HeFH inadequately controlled with statins.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03510884.
UNASSIGNED: To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The primary end point was percent change in LDL-C from baseline to week 24 in each cohort.
UNASSIGNED: Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9%] female), alirocumab showed statistically significant reductions in LDL-C vs placebo in both cohorts at week 24. Least squares mean difference in percentage change from baseline was -43.3% (97.5% CI, -56.0 to -30.7; P < .001) Q2W and -33.8% (97.5% CI, -46.4 to -21.2; P < .001) Q4W. Hierarchical analysis of secondary efficacy end points demonstrated significant improvements in other lipid parameters at weeks 12 and 24 with alirocumab. Two patients receiving alirocumab Q4W experienced adverse events leading to discontinuation. No significant difference in adverse event incidence was observed between treatment groups. Open-label period findings were consistent with the double-blind period.
UNASSIGNED: The findings in this study indicate that alirocumab Q2W or Q4W significantly may be useful for reducing LDL-C and other lipid parameters and be well tolerated in pediatric patients with HeFH inadequately controlled with statins.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03510884.
摘要：
■许多患有杂合子家族性高胆固醇血症（HeFH）的儿科患者单用他汀类药物无法达到推荐的低密度脂蛋白胆固醇（LDL-C）浓度，需要辅助降脂治疗（LLT）；在儿科患者中使用alirocumab需要评估。
■评估alirocumab在HeFH控制不充分的儿科患者中的疗效。
■这是一项3期随机临床试验，于2018年5月至2022年8月在24个国家的43个中心进行。8至17岁的HeFH儿科患者，LDL-C130mg/dL或更高，和接受他汀类药物或其他LLTs的包括在内。在连续纳入给药队列后，每2周筛选给药的99名患者中的25名(Q2W)未能筛选;每4周筛选给药的104名患者中的25名(Q4W)未能筛选。共有74例Q2W患者中的70例(95%)和79例Q4W患者中的75例(95%)完成了双盲期。
■患者被随机2：1接受皮下alirocumab或安慰剂和Q2W或Q4W。剂量基于体重（如果<50kg，则Q2W为40mg或Q4W为150mg；如果≥50kg，则Q2W为75mg或Q4W为300mg），如果LDL-C在第8周为110mg/dL或更高，则在第12周调整。24周双盲期后,患者可在80周开放标签期内接受alirocumab治疗.
主要终点是每个队列中LDL-C从基线到第24周的变化百分比。
■在153名随机接受alirocumab或安慰剂的患者中（平均[范围]年龄，12.9[8-17]岁；87[56.9%]女性)，在第24周时,在两个队列中,与安慰剂相比,alirocumab的LDL-C显著降低.与基线相比的百分比变化的最小二乘平均差异为-43.3％（97.5％CI，-56.0至-30.7；P<.001）Q2W和-33.8％（97.5％CI，-46.4至-21.2；P<.001）Q4W。次要疗效终点的层次分析表明，在12周和24周时，alirocumab的其他脂质参数显着改善。两名接受alirocumabQ4W的患者经历了导致停药的不良事件。治疗组之间不良事件发生率无显著差异。开放标签期发现与双盲期一致。
■这项研究的结果表明，alirocumabQ2W或Q4W可显著用于降低LDL-C和其他脂质参数，并且在他汀类药物控制不足的HeFH儿科患者中具有良好的耐受性。
■ClinicalTrials.gov标识符：NCT03510884。
■评估alirocumab在HeFH控制不充分的儿科患者中的疗效。
■这是一项3期随机临床试验，于2018年5月至2022年8月在24个国家的43个中心进行。8至17岁的HeFH儿科患者，LDL-C130mg/dL或更高，和接受他汀类药物或其他LLTs的包括在内。在连续纳入给药队列后，每2周筛选给药的99名患者中的25名(Q2W)未能筛选;每4周筛选给药的104名患者中的25名(Q4W)未能筛选。共有74例Q2W患者中的70例(95%)和79例Q4W患者中的75例(95%)完成了双盲期。
■患者被随机2：1接受皮下alirocumab或安慰剂和Q2W或Q4W。剂量基于体重（如果<50kg，则Q2W为40mg或Q4W为150mg；如果≥50kg，则Q2W为75mg或Q4W为300mg），如果LDL-C在第8周为110mg/dL或更高，则在第12周调整。24周双盲期后,患者可在80周开放标签期内接受alirocumab治疗.
主要终点是每个队列中LDL-C从基线到第24周的变化百分比。
■在153名随机接受alirocumab或安慰剂的患者中（平均[范围]年龄，12.9[8-17]岁；87[56.9%]女性)，在第24周时,在两个队列中,与安慰剂相比,alirocumab的LDL-C显著降低.与基线相比的百分比变化的最小二乘平均差异为-43.3％（97.5％CI，-56.0至-30.7；P<.001）Q2W和-33.8％（97.5％CI，-46.4至-21.2；P<.001）Q4W。次要疗效终点的层次分析表明，在12周和24周时，alirocumab的其他脂质参数显着改善。两名接受alirocumabQ4W的患者经历了导致停药的不良事件。治疗组之间不良事件发生率无显著差异。开放标签期发现与双盲期一致。
■这项研究的结果表明，alirocumabQ2W或Q4W可显著用于降低LDL-C和其他脂质参数，并且在他汀类药物控制不足的HeFH儿科患者中具有良好的耐受性。
■ClinicalTrials.gov标识符：NCT03510884。
