MULTI-CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II STUDY OF AEROSOLIZED TG

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的目的是证实在最近完成的一项使用tgAAVCF(25B01，明尼苏达大学GCRC#819)的多剂量气溶胶研究中观察到的肺功能和细胞因子水平的改善。TgAAVCF正在被开发为治疗CF的基因疗法，之前完成的第二阶段研究显示出良好的安全性和轻微、短期的肺功能改善。拟议的研究旨在检测FEV1的变化，类似于在第30天多剂量气雾剂试验中观察到的变化，但将在其他时间点进行类似的肺功能分析，以确定两剂研究药物后肺功能变化的时间进程和持久性。这将是一项随机、双盲、安慰剂对照试验，比较雾化tgAAVCF与匹配的安慰剂。研究药物将在两个不同的场合服用，相隔一个月。受试者将参与这项研究，为期224天，在首次服用研究药物后150天和210天内，每2周前往明尼苏达大学综合临床研究中心(GCRC)进行临床访问，共8次，并进行电话随访。登记参加试验的受试者将被要求在GCRC完成筛查访问，以验证进入标准，然后将被随机分配到雾化tgAAVCF或匹配的安慰剂。受试者将在2周后返回GCRC进行肺功能测试、诱导痰和血清抗体测试。两周后，受试者将返回服用第二剂，也是最后一剂研究试剂。在接下来的两个月里，受试者将每两周在GCRC接受一次检查。受试者将在最后一次就诊后2个月和4个月通过电话联系，以评估任何不良事件。

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. The purpose of this study is to confirm the improvement in pulmonary function and cytokine levels observed in a recently completed multidose aerosol study with tgAAVCF (25B01, University of Minnesota GCRC #819). tgAAVCF is being developed as Gene Therapy for CF and the previously completed Phase II study showed a good safety profile and mild, short-term improvement in pulmonary function. The proposed study is powered to detect changes in FEV1 similar to those observed in the multidose aerosol trial at Day 30, but similar analyses of pulmonary function will be conducted at other time points to determine the time course and durability of changes in pulmonary function after two doses of study drug. This will be a randomized, double blind, placebo controlled trial of aerosolized tgAAVCF versus matching placebo. Study drug will be administered on 2 separate occasions, one month apart. Subjects participation in the study will be for a total of 224 days, with clinic visits to the General Clinical Research Center (GCRC) of the University of Minnesota every 2 weeks for a total of 8 visits and phone follow up 150 and 210 days after first administration of study drug. Subjects enrolled into the trial will be asked to complete a screening visit at the GCRC to verify entry criteria and then will be randomized to either aerosolized tgAAVCF or matching placebo. Subjects will return to the GCRC 2 weeks later for pulmonary function testing, induced sputum, and serum antibodies testing. Two weeks later the subjects will return for a second, and last, dose of study agent. Subjects will then be seen at the GCRC every 2 weeks for the next 2 months. Subjects will be contacted by phone 2 and 4 months after the last visit to assess for any adverse events.