MYOZYME TEMPORARY ACCESS PROGRAM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 假设：美而赞输注给药将使庞贝氏症患者的总体状况显著改善。 美而赞临时使用计划旨在为美国（US）的庞贝氏症成人患者提供美而赞的有限时间使用权，美而赞采用扩大规模的生产工艺生产，直至美国食品药品监督管理局（FDA）批准该规模的生产用于商业用途。迄今为止，通过该放大工艺生产的美而赞已用于其他临床研究，包括正在晚发性庞贝氏症患者中进行的临床试验（AGLU 02704）和美国以外的所有商业患者。 与重组蛋白生产的情况一样，该工艺以较小的体积开发，优化，随后扩大规模以生产更大的体积。Genzyme正在通过补充现有的美而赞生物制剂许可申请，寻求通过扩大生产工艺生产的产品的许可。根据美而赞的完整处方信息，所有患者将接受美而赞20 mg/kg剂量静脉（IV）给药，每隔一周一次。根据体重变化，可根据需要调整美而赞给药总量。此外，治疗医生可自行决定按理想体重给药，以及在程序过程中降低剂量。将根据要求的评估时间表进行安全性和疗效评估。 独立的数据安全性监查委员会（DSMB）和独立的过敏反应审查委员会（ARRB）将审查安全性信息。将收集并记录筛选评估数据：患者人口统计学、病史，包括庞贝氏症的诊断和临床体征和症状，以及有生育能力女性的筛选尿妊娠试验。将记录根据该计划首次输注后发生的所有不良事件，包括非严重AE、严重AE和输注相关反应以及输注前的任何治疗前药物和AE发生时的合并用药。抗重组人酸？-将记录葡萄糖苷酶（rhGAA）免疫球蛋白G（IgG）抗体滴度（根据该计划首次输注前、每3个月一次和患者完成该计划时）以及在复发或中度至重度IAR后进行的任何专业免疫学检查。将记录所有美而赞输注的次数和间隔，并记录任何遗漏、部分或中断的输注、原因以及用于治疗输注相关反应的药物或其他医疗措施。呼吸机使用，包括任何新的有创呼吸机使用或每天使用小时数的变化，将通过患者日记记录并输入数据库。将记录在根据该计划首次输注前、此后每6个月以及患者完成该计划时使用庞贝氏症儿科评估和残疾量表（PEDI）进行的运动评估。除了所需的评估外，参与医生将根据患者的个性化医疗护理和常规随访需求确定额外评估的频率。

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. Hypothesis: The Administration of Myozyme Infusions will elicit significantly marked improvements in Pompe patients overall condition. The objective of the Myozyme Temporary Access Program is to provide adult patients with Pompe disease in the United States (US) access to Myozyme produced from a scaled-up manufacturing process for a limited time until production at this scale is approved for commercial use by the Food and Drug Administration (FDA). Myozyme produced via this scaled-up process has been used in other clinical studies to date, including the ongoing clinical trial in patients with late-onset Pompe disease (AGLU02704) and by all commercial patients outside the US. As is often the case with recombinant protein manufacture, the process was developed at a smaller volume, optimized, and subsequently scaled-up to produce larger volumes. Genzyme is pursuing licensure of product produced from the scaled-up manufacturing process via a supplement to the existing Biologics License Application for Myozyme. All patients will receive Myozyme at a dose of 20 mg/kg administered intravenously (IV) once every other week according to the full prescribing information for Myozyme. The total amount of Myozyme administered may be adjusted as needed to account for changes in body weight. In addition, the treating physician has the discretion to dose by ideal weight, as well as to lower the dosage during the course of the program. Safety and efficacy assessments will be performed in accordance with the Required Schedule of Assessments. An independent Data Safety Monitoring Board (DSMB) and an independent Allergic Reaction Review Board (ARRB) will review safety information. Data on screening assessments will be collected and recorded: patient demographics, medical history, including diagnosis and clinical signs and symptoms of Pompe disease, and screening urine pregnancy testing for women of childbearing potential. The occurrence of all adverse events from the time of first infusion under this program, including non-serious AE's, serious AE's and infusion associated reactions as well as any pre-treatment medications prior to infusion and concomitant medications at the time of an AE will be recorded. Anti-recombinant human acid ?-glucosidase (rhGAA) immunoglobulin G (IgG) antibody titers (prior to first infusion under this program, every 3 months, and at a patient's completion of the program) and any specialty immunologic testing performed following recurrent or moderate to severe IAR's will be recorded. The number and interval of all Myozyme infusions will be documented, noting any missed, partial, or interrupted infusions, the reasons therefore, and medications or other medical measures used to treat infusion-related reactions. Ventilator use, including any new invasive ventilator use or changes in hours of use per day, will be recorded via patient diary and entered in to the database. Motor assessments, performed using the Pompe Pediatric Evaluation and Disability Inventory (PEDI) prior to the first infusion under this program, every 6 months thereafter, and at a patient's completion of the program, will be documented. Beyond the required assessments, participating physicians will determine the frequency of additional assessments according to their patients individualized needs for medical care and routine follow-up.