The Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa.

IF 3.9 2区医学 Q1 PEDIATRICS

Journal of Pediatrics Pub Date : 2025-05-29 DOI:10.1016/j.jpeds.2025.114664

David Kronn, James Davison, Alexander Broomfield, Anaïs Brassier, François Labarthe, Si Houn Hahn, Satoko Kumada, Hirotaka Ohki, Sasapin Grace Prakalapakorn, Catherine Wilson, Kristina An Haack, Olivier Huynh-Ba, Susan Richards, Susan Sparks, Swathi Tammireddy, Tianyue Zhou, Yin-Hsiu Chien, Priya S Kishnani

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引用次数: 0

Abstract

Objective: To evaluate long-term safety and efficacy of avalglucosidase alfa in children with infantile-onset Pompe disease (IOPD) experiencing clinical decline (cohorts 1 and 2) or suboptimal response (cohort 3) to pre-study alglucosidase alfa.

Study design: The Mini-COMET clinical trial, a phase 2, open-label, ascending-dose, 3-cohort study, has a 25-week primary analysis period (PAP) and an extension treatment period (ETP). In the PAP, cohorts 1 (n=6) and 2 (n=5) received avalglucosidase alfa 20 or 40 mg/kg every other week (qow), respectively. Cohort 3 received avalglucosidase alfa 40 mg/kg qow (n=5) or alglucosidase alfa (pre-study [>6 months] stable dose: 20 mg/kg qow to 40 mg/kg weekly; n=6). All children completed the PAP and entered the ETP. Children receiving avalglucosidase alfa in the PAP continued the same dose in the ETP. Those receiving alglucosidase alfa in the PAP received avalglucosidase alfa 40 mg/kg qow in the ETP.

Results: At baseline, children were 1-12 years old. Interim data (≥97 weeks) are presented from all 22 children, 20 receiving avalglucosidase alfa 40 mg/kg qow and 2 receiving 20 mg/kg qow in the ETP. Among the 6 who received 20 mg/kg qow avalglucosidase alfa in PAP (cohort 1), 4 had their dose increase to 40 mg/kg qow because of further clinical decline in the ETP. No child died or discontinued at data cut-off. PAP and ETP safety profiles were similar; no treatment-related serious or severe treatment-emergent adverse events occurred. Avalglucosidase alfa was well-tolerated, with no increased safety risk or immunogenicity concerns post-treatment switch. Echocardiography revealed persistent left-ventricular mass Z-score normalization. Compared with baseline, biomarkers of Pompe disease burden decreased, and motor function improved or stabilized.

Conclusion: Results support the positive clinical impact of long-term avalglucosidase alfa in children with IOPD.

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Mini-COMET临床试验：Avalglucosidase Alfa治疗97周后婴儿起病庞贝病患儿的安全性和有效性

目的：评价α α葡萄糖苷酶在临床衰退（队列1和2）或对α α葡萄糖苷酶预研究反应不佳（队列3）的婴儿期Pompe病（IOPD）患儿中的长期安全性和有效性。研究设计：Mini-COMET临床试验是一项2期、开放标签、递增剂量、3队列研究，初始分析期（PAP）为25周，延长治疗期（ETP）为25周。在PAP中，队列1 （n=6）和队列2 （n=5）每隔一周（qow）分别接受avalglucosidase alfa 20或40mg /kg。队列3接受α葡糖苷酶40 mg/kg /次（n=5）或α葡糖苷酶(研究前[6个月]稳定剂量：20 mg/kg /次至40 mg/kg每周；n = 6)。所有的孩子都完成了PAP并进入了ETP。在PAP组中接受阿瓦葡萄糖苷酶治疗的儿童在ETP组中继续给予相同剂量。在PAP中接受α α葡萄糖苷酶治疗的患者在ETP中每天接受α α葡萄糖苷酶40 mg/kg。结果：基线时，儿童年龄为1-12岁。所有22名儿童提供了中期数据（≥97周），其中20名在ETP中接受阿瓦葡萄糖苷酶α 40 mg/kg的剂量，2名接受20 mg/kg的剂量。在6名接受PAP治疗的患者中（队列1），由于临床ETP进一步下降，4名患者的剂量增加到40 mg/kg。在数据截止时，没有儿童死亡或停药。PAP和ETP的安全性相似；未发生与治疗相关的严重或严重治疗引起的不良事件。Avalglucosidase alfa耐受性良好，治疗后切换没有增加的安全风险或免疫原性问题。超声心动图显示左心室质量z评分持续正常化。与基线相比，Pompe病负担的生物标志物减少，运动功能改善或稳定。结论：结果支持长期应用α葡糖苷酶治疗儿童IOPD的积极临床效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pediatrics 医学-小儿科

CiteScore

6.00

自引率

2.00%

发文量

696

审稿时长

31 days

期刊介绍： The Journal of Pediatrics is an international peer-reviewed journal that advances pediatric research and serves as a practical guide for pediatricians who manage health and diagnose and treat disorders in infants, children, and adolescents. The Journal publishes original work based on standards of excellence and expert review. The Journal seeks to publish high quality original articles that are immediately applicable to practice (basic science, translational research, evidence-based medicine), brief clinical and laboratory case reports, medical progress, expert commentary, grand rounds, insightful editorials, “classic” physical examinations, and novel insights into clinical and academic pediatric medicine related to every aspect of child health. Published monthly since 1932, The Journal of Pediatrics continues to promote the latest developments in pediatric medicine, child health, policy, and advocacy. Topics covered in The Journal of Pediatrics include, but are not limited to: General Pediatrics Pediatric Subspecialties Adolescent Medicine Allergy and Immunology Cardiology Critical Care Medicine Developmental-Behavioral Medicine Endocrinology Gastroenterology Hematology-Oncology Infectious Diseases Neonatal-Perinatal Medicine Nephrology Neurology Emergency Medicine Pulmonology Rheumatology Genetics Ethics Health Service Research Pediatric Hospitalist Medicine.