7.0 INVESTIGATIONAL PLAN 
7.1 Entry 
Eligible patients will be admitted to the Pediatric Clinical Research Unit, a part of The 
Johns Hopkins General Clinical Research Center (GCRC) for 18 days for performance of 
the baseline study, vehicle administration, and vector administration protocols, and will be 
maintained on respiratory vims precautions (isolation with gown, mask, and gloves) 
during the entire period. During their entire inpatient stay, patients will be treated with 
intravenous antibiotics and chest physiotherapy (three times daily), in order to optimize 
their ability to tolerate multiple bronchoscopies and other procedures. Antibiotic coverage 
will consist of two agents selected based on sensitivity studies of the patient's most recent 
sputum culture, one of which will generally be an anti-pseudomonal aminoglycoside. 
Patients will be screened at admission for infectious adenovirus and infectious AAV and if 
either of these agents is isolated, the patient will be released and rescheduled for at least one 
month after the infection. Patients will have all current medications, including DNase, 
continued during the study, and participation will be postponed if any changes in their 
medication regimen have occurred in the 2 weeks preceding the study. Standardization of 
DNase dosing schedule with respect to vector instillation will be attempted. 
7.2 Study Cohorts 
This study will include 8 cohorts of 2 patients each. Vector administration to each cohort 
will be staggered by at least one month, and vector administration to patients within each 
cohort will be staggered by at least one week to allow for evaluation of acute toxicity. The 
dosing schedule for the cohorts is shown below; doses are given as tgAAVCF vector 
particles: 
Site 
Group 
Group 
Group 
Group 
Group 
Group 
Group 
Group 
1 
2 
3 
4 
5 
6 
7 
8 
Nasal 
1X10 6 
1X10 7 
3X10 7 
1X10 8 
3X10 8 
1X10 9 
1X10 9 
1X10 9 
RLL 
1X10 7 
3X10 7 
1X10 8 
3X10 8 
1X10 9 
3X10 9 
1X101° 
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