Che potential difference is approximately 50% that of individuals with CF. 
The bronchial potential difference assessment is currently being worked out. 
The technique is similar to that used for nasal potential difference (53, 54) 
except there is the problem that the local anesthesia used for the bronchos- 
copy procedure blocks the Na* channels (and may have other changes as well) . 
Part A. Part A is designed to evaluate the safety of and the pharmacodynamics 
of expression of CFTR mRNA directed by a single administration of the vector 
in the respiratory epithelium. Seven groups of patients will be evaluated in 
part A, with n=2 in each group (i.e., a total of 14 individuals will be stud- 
ied in group A). The total number of 14 individuals is justified by the need 
for 2 patients/dose group to reproducibly assess safety and biologic efficacy 
and by the need to increase the dose slowly. Each individual will serve as 
their own control, by comparing parameters in the initial baseline period and 
the vehicle control period to the Ad^vCFTR.lO treatment period. The study in- 
dividuals may go through the baseline period and vehicle control period at any 
time prior to entering the Ad^CFTR-lO treatment period, but if the time 
between the end of the vehicle control period and beginning of the treatment 
period is greater than 2 months, an additional day 1 (except for the CT scan, 
see Appendix A5.1) baseline evaluation will be carried out within 10 days 
prior to starting the treatment. In the description of baseline, vehicle con- 
trol, and AdcvCFTR.10 treatment periods that follows, there is an accompanying 
time chart that details the time for assessment of various safety and efficacy 
parameters. A list of the parameters within each category are in section 5.1 
and the abbreviations used can be found in Appendix A3 . 
6.1 Baseline Period/Part A. Prior to start of the baseline period, there will 
be an initial evaluation to examine safety and efficacy parameters. This data, 
plus the data gathered throughout the baseline period will determine if the 
individual is eligible to continue in the protocol (see Inclusion and Exclu- 
sion criteria, section 4). If eligible for the remainder of the protocol, the 
individual will enter the vehicle control period within 3 months following the 
completion of the baseline period. Following the initial evaluation, the base- 
line period will include a 2-3 day inpatient evaluation and outpatient evalua- 
tion. The baseline period will be used to evaluate the reproducibility of var- 
ious parameters as well as the ability of the individual to meet the inclu- 
sion/exclusion criteria. 
6.2 Vehicle Control Period/Part A. The vehicle control period will be to eval- 
uate the same safety and efficacy parameters evaluated in the baseline period, 
except that the vehicle to be used in the Ad^vCFTR-lO preparation will be ad- 
ministered to the bronchi in a fashion identical to that in the Ad^vCFTR-lO 
treatment period. The vehicle control period will include a 2-3 day inpatient 
evaluation and outpatient evaluation. The individual must enter the vehicle 
control period within 3 months of completing the baseline period. If the time 
since ending the baseline period is greater than this period, there will be a 
reassessment of the safety and efficacy parameters as detailed in above. 
6.3 Ad^vCFTR.10 Experimental Treatment Period/Part A. The 7 groups will be 
used to evaluate ascending doses of the vector, from 10 6 to 10 9 pfu/site (in 
1/2 log increments). Each individual will receive 3 doses (during the same 
bronchoscopy procedure), in three different sites in the same lung at the lev- 
el just distal to the lobar bronchi (i.e., the total dose for each patient in 
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