RECOMBINANT HUMAN ACID ALPHA-GLUCOSIDASE IN PTS W/ INFANTILE-ONSET POMPE DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项开放标签的多中心研究，重组人酸性α -葡萄糖苷酶（rhGAA）（也称为肌酶）作为酶替代疗法治疗6至36个月大的婴儿起病庞贝病。这是一种罕见的疾病，在所有表型的庞贝病中，计算发病率为1 / 40,000。主要目标是：1)评估rhGAA的安全性；2)确定在治疗过程中存活的患者比例；3)确定rhGAA在该人群中的药动学特征；4)测定rhGAA的药效学。受试者每两周静脉输注20 mg/kg rhGAA，共52周；然而，如果患者在治疗至少26周后符合剂量增加标准，则剂量可以增加到最大40mg /kg。然后，患者将在重复的52周维持模块中继续治疗，可重复（如果没有患者安全问题），直到研究终止或直到市场批准。临床反应的心脏、呼吸和运动评估将用于确定剂量增加的适宜性。在初始阶段，将在基线、第12周和第52周进行肌肉活检。在维持期的每一年结束时，由研究者自行决定是否进行肌肉活检。总共20名受试者将被纳入研究，其中只有1名处于研究维护阶段的受试者出现在现场。受试者将每两周在GCRC上看到一次输注。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an open-label, multicenter study of recombinant human acid alpha-glucosidase (rhGAA) (also called Myozyme) as an enzyme replacement therapy for the treatment of infantile-onset Pompe disease in patients 6 to 36 months old. This is a rare disease with a calculated incidence of 1 in 40,000 for all phenotypes of Pompe disease. The primary objectives are: 1) to evaluate the safety profile of rhGAA; 2) to determine the proportion of patients who are alive over the course of treatment; 3) to determine the pharmacokinetic profile of rhGAA in this population; and 4) to determine the pharmacodynamics of rhGAA. Subjects will receive 20 mg/kg rhGAA by intravenous infusion every two weeks for 52 weeks; however the dose may be increased to a maximum of 40 mg/kg if a patient meets the dose augmentation criteria after at least 26 weeks of treatment. Patients will then continue treatment in a repeating 52-week maintenance module, repeatable (if there are no patient safety concerns) until the study is terminated or until market approval. Cardiac, respiratory, and motor assessments of clinical response will be used to determine suitability for dose augmentation. Muscle biopsy will be performed at baseline, week 12, and week 52 during the initial phase. There is an optional muscle biopsy at the end of each year of the maintenance phase, at the discretion of the investigator. A total of 20 subjects will be enrolled with only 1 subject, who is in the maintenance phase of the study, to be seen at this site. The subject will be seen on the GCRC for the infusions every 2 weeks.