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

重组人酸性α-葡萄糖苷酶在患有婴儿型庞贝病的PTS中的应用

• 批准号: 7378071
• 负责人: SHAWN E MCCANDLESS
• 金额: $ 0.27万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378071
• 关键词: RECOMBINANT; HUMAN; ACID; ALPHA; GLUCOSIDASE

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项在6至36个月大的患者中开展的关于重组人酸性α-葡萄糖苷酶（rhGAA）（也称为Myozyme）作为酶替代疗法治疗起病型庞贝氏症的开放标签、多中心研究。这是一种罕见疾病，所有庞贝氏症表型的计算发病率为1/40，000。主要目标是：1）评价rhGAA的安全性特征; 2）确定在治疗过程中存活的患者比例; 3）确定rhGAA在该人群中的药代动力学特征;以及4）确定rhGAA的药效学。受试者将接受20 mg/kg rhGAA静脉输注，每2周一次，持续52周;然而，如果患者在至少26周治疗后符合剂量增加标准，则剂量可增加至最大40 mg/kg。然后，患者将在重复的52周维持模块中继续治疗，可重复（如果没有患者安全性问题），直至研究终止或上市批准。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用性。在初始阶段，将在基线、第12周和第52周进行肌肉活检。根据研究者的判断，在维持阶段的每年年底进行可选的肌肉活检。共入组20例受试者，仅1例受试者将在该研究中心接受观察，该受试者处于研究的维持阶段。将在GCRC上查看受试者的输注情况，每2周一次。