MYOZYME TEMPORARY ACCESS PROGRAM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 假设：给予Myozyme输液将显著改善Pompe患者的整体情况。 Myozyme临时访问计划的目标是为美国(US)的庞培病成年患者提供有限时间内从扩大生产过程中生产的Myozyme，直到这种规模的生产获得食品和药物管理局(FDA)批准用于商业用途。到目前为止，通过这种放大过程生产的Myozyme已被用于其他临床研究，包括正在进行的晚发型庞贝病患者的临床试验(AGLU02704)和美国以外的所有商业患者。 就像通常的重组蛋白质生产一样，该工艺是以较小的体积开发的，经过优化，然后放大以生产更大的体积。Genzyme正在通过补充现有的Myozyme生物制品许可证申请，寻求从扩大的制造过程中生产的产品获得许可。所有患者将根据Myozyme的完整处方信息，每隔一周静脉注射20 mg/kg的Myozyme。肌酶的总量可以根据需要进行调整，以适应体重的变化。此外，治疗医生有权酌情按理想体重剂量，以及在计划过程中降低剂量。将按照规定的评估时间表进行安全性和有效性评估。 一个独立的数据安全监测委员会(DSMB)和一个独立的过敏反应审查委员会(ARRB)将审查安全信息。将收集和记录关于筛查评估的数据：患者人口统计数据、病史，包括庞贝病的诊断和临床体征和症状，以及为有生育潜力的妇女筛查尿液怀孕测试。根据本计划，从第一次输液起发生的所有不良事件，包括非严重的AE、严重的AE和输液相关反应，以及输液前的任何前处理药物和AE发生时的伴随药物，都将被记录下来。将记录抗重组人酸性葡萄糖苷酶(RhGAA)免疫球蛋白G(Ig G)抗体效价(在本计划下第一次输液前、每3个月一次以及在患者完成计划时)以及在复发或中至重度IAR后进行的任何特殊免疫学测试。所有Myozyme输液的次数和间隔将被记录下来，并注明任何遗漏的、部分的或中断的输液、原因以及用于治疗输液相关反应的药物或其他医学措施。呼吸机的使用，包括任何新的有创呼吸机的使用或每天使用小时的变化，将通过患者日记记录并输入数据库。在根据该计划进行第一次输液之前、之后每6个月以及在患者完成该计划时，使用庞培儿童评估和残疾评估(PEDI)进行的运动评估将被记录下来。除了所需的评估外，参与的医生还将根据患者对医疗护理和常规随访的个性化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.