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

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来源获得了主要资金，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。本研究的目的是证实在最近完成的tgAAVCF多剂量气雾剂研究（25 B 01，University of Minnesota GCRC #819）中观察到的肺功能和细胞因子水平的改善。tgAAVCF正在开发作为CF的基因疗法，先前完成的II期研究显示出良好的安全性和肺功能的轻度短期改善。拟定研究有把握度检测第30天FEV 1的变化，该变化与多次给药气雾剂试验中观察到的变化相似，但将在其他时间点进行类似的肺功能分析，以确定两次研究药物给药后肺功能变化的时间过程和持久性。这将是雾化tgAAVCF与匹配安慰剂的随机、双盲、安慰剂对照试验。研究药物将在2个不同的时间给药，间隔1个月。受试者将参与研究共224天，每2周一次到明尼苏达大学的一般临床研究中心（GCRC）进行临床访视，共8次访视，并在研究药物首次给药后150天和210天进行电话随访。将要求入组试验的受试者在GCRC完成筛选访视以验证入选标准，然后将随机分配至雾化tgAAVCF或匹配安慰剂组。受试者将在2周后返回GCRC进行肺功能检测、诱导痰和血清抗体检测。两周后，受试者将返回接受第二次（也是最后一次）研究药物给药。然后，在接下来的2个月内，每2周一次在GCRC对受试者进行访视。将在末次访视后2个月和4个月通过电话联系受试者，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.