Abstract：
Symptoms of hereditary angioedema (HAE) often first occur during childhood, and HAE attacks in children can be severe and substantially affect health-related quality of life (HRQoL). However, there are no approved long-term prophylaxis treatments for children aged less than 6 years.
The SPRING Study (NCT04070326) evaluated the safety, pharmacokinetics, and efficacy of lanadelumab and HRQoL in patients aged 2 to less than 12 years.
Over 52 weeks of treatment, patients aged 2 to less than 6 years received lanadelumab 150 mg every 4 weeks (Q4W) and patients aged 6 to less than 12 years received 150 mg every 2 weeks (Q2W) but could switch to Q4W if they were attack-free for 26 weeks.
We enrolled 21 patients (aged 2 to less than 6 years: n = 4; aged 6 to less than 12 years: n = 17), 20 of whom completed the study. There were no reported serious treatment-emergent adverse events or discontinuations resulting from such events. Treatment-emergent adverse events were reported for 17 patients (81.0%). The most common TEAE was injection site pain. Overall systemic exposure was comparable for both age groups. The mean (SD) attack rate during treatment decreased by 94.8% from baseline (1.84 [1.53] to 0.08 [0.17] attacks/mo), and 16 (76.2%) patients were attack-free. The attack rate reduction in both age groups was similar during the first 26-week fixed-dosing treatment. Seven patients switched from Q2W to Q4W and remained attack-free. A large, clinically meaningful increase in the Pediatric Quality of Life Inventory Generic Core Scale Total Score and a large increase in the Pediatric Quality of Life Inventory Generic Core Scale-Family Impact Module Total Score from baseline to end of study (better HRQoL) were observed.
Findings support safety, efficacy, and improved HRQoL with lanadelumab 150 mg Q2W and Q4W regimens for the prevention of HAE attacks in patients aged 2 to less than 12 years.
The SPRING Study (NCT04070326) evaluated the safety, pharmacokinetics, and efficacy of lanadelumab and HRQoL in patients aged 2 to less than 12 years.
Over 52 weeks of treatment, patients aged 2 to less than 6 years received lanadelumab 150 mg every 4 weeks (Q4W) and patients aged 6 to less than 12 years received 150 mg every 2 weeks (Q2W) but could switch to Q4W if they were attack-free for 26 weeks.
We enrolled 21 patients (aged 2 to less than 6 years: n = 4; aged 6 to less than 12 years: n = 17), 20 of whom completed the study. There were no reported serious treatment-emergent adverse events or discontinuations resulting from such events. Treatment-emergent adverse events were reported for 17 patients (81.0%). The most common TEAE was injection site pain. Overall systemic exposure was comparable for both age groups. The mean (SD) attack rate during treatment decreased by 94.8% from baseline (1.84 [1.53] to 0.08 [0.17] attacks/mo), and 16 (76.2%) patients were attack-free. The attack rate reduction in both age groups was similar during the first 26-week fixed-dosing treatment. Seven patients switched from Q2W to Q4W and remained attack-free. A large, clinically meaningful increase in the Pediatric Quality of Life Inventory Generic Core Scale Total Score and a large increase in the Pediatric Quality of Life Inventory Generic Core Scale-Family Impact Module Total Score from baseline to end of study (better HRQoL) were observed.
Findings support safety, efficacy, and improved HRQoL with lanadelumab 150 mg Q2W and Q4W regimens for the prevention of HAE attacks in patients aged 2 to less than 12 years.
摘要：
背景：遗传性血管性水肿（HAE）的症状通常首先发生在儿童时期，儿童HAE发作可能很严重，并严重影响与健康相关的生活质量（HRQoL）。然而,对于6岁以下的儿童，没有批准的长期预防治疗。
目的：SPRING研究（NCT04070326）评估了安全性，药代动力学，lanadelumab和HRQoL在2<12岁患者中的疗效。
方法：超过52周的治疗，2-<6岁的患者每4周(Q4W)接受lanadelumab150mg,6-<12岁的患者每2周(Q2W)接受150mg,但如果26周无发作,则可切换至Q4W.
结果：纳入21名患者（2-<6年：n=4；6-<12年：n=17），n=20完成研究。没有报告严重的因治疗引起的不良事件（TEAE）或因TEAE而中断。17例（81.0%）患者报告TEAE；最常见的TEAE是注射部位疼痛。两个年龄组的总体全身暴露量具有可比性。治疗期间平均(SD)发作率从基线下降94.8%(1.84[1.53]至0.08[0.17]发作/月),16例(76.2%)患者无发作。在第一个26周的固定剂量治疗期间，两个年龄组的发作率降低相似。7名患者从Q2W切换到Q4W，并且没有发作。一个大的，从基线到研究结束,观察到PedsQL总分有临床意义的增加和PedsQL-FIM总分的大幅增加(HRQoL较好).
结论：研究结果支持安全性，功效,lanadelumab150mgQ2W和Q4W方案用于预防2-<12岁患者的HAE发作，并改善HRQoL。
目的：SPRING研究（NCT04070326）评估了安全性，药代动力学，lanadelumab和HRQoL在2<12岁患者中的疗效。
方法：超过52周的治疗，2-<6岁的患者每4周(Q4W)接受lanadelumab150mg,6-<12岁的患者每2周(Q2W)接受150mg,但如果26周无发作,则可切换至Q4W.
结果：纳入21名患者（2-<6年：n=4；6-<12年：n=17），n=20完成研究。没有报告严重的因治疗引起的不良事件（TEAE）或因TEAE而中断。17例（81.0%）患者报告TEAE；最常见的TEAE是注射部位疼痛。两个年龄组的总体全身暴露量具有可比性。治疗期间平均(SD)发作率从基线下降94.8%(1.84[1.53]至0.08[0.17]发作/月),16例(76.2%)患者无发作。在第一个26周的固定剂量治疗期间，两个年龄组的发作率降低相似。7名患者从Q2W切换到Q4W，并且没有发作。一个大的，从基线到研究结束,观察到PedsQL总分有临床意义的增加和PedsQL-FIM总分的大幅增加(HRQoL较好).
结论：研究结果支持安全性，功效,lanadelumab150mgQ2W和Q4W方案用于预防2-<12岁患者的HAE发作，并改善HRQoL。
