Patient 
# 
Dose 
at 
each 
site 
it of 
sites of 
admin- 
istra- 
tion 
Sites 
Interval 
between 
doses 
Total dose 
to be admin- 
istered 
every 30 
days 
Total # of 
times of 
admin- 
istration 
8A , 8B , 
8C , 8D 
lxlO 7 
3 
Each site in 
same lung, 
each just dis- 
tal to lobar 
bronchus, same 
sites every 30 
days 
30 days 
3xl0 7 
6 for 180d 
total 
9A, 9B , 
9C , 9D 
1x10® 
3 
same 
30 days 
3x10® 
same 
10A.10B, 
10C , 10D 
1x10® 
3 
same 
30 days 
3xl0 9 
same 
For each site, for each dose (every 30 days), the estimated MOI is 1.8 to 180. 
The assessments of vector-directed expression will be at intervals after each 
dose as specified in the time line in Appendix A5 . 6 . 
8. Part C. Part C is designed to evaluate the pattern of expression following 
repeat administration at a dose higher than the initial dose. The underlying 
concept of the use of a higher dose is that local immunity may be sufficient 
to prevent expression following repeat dosing at the same dose, but might be 
overcome at a higher dose such that expression would be observed. The patients 
in part C will include all patients in part A (i.e., all patients from part A 
will move to part C; no new patients will be entered). 
8.1 AdcvCFTR.10 Treatment Period/Part C. Since part C is an extension of part 
A, there will be no separate baseline and vehicle control period for part C. 
The dose to be used will be 1 log higher than that used in part A, but no 
higher than 10 9 pfu. The repeat dosing will be at 90 days and at 180 days from 
the initial dose administered in part A (or longer, depending on the pharmaco- 
dynamics of expression observed in part B) . No patient will be entered into 
part C until the dose to be used in part C has already been evaluated in 2 
patients in part A. Part C will not extend beyond 180 days. The interval be- 
tween starting individuals in part C will be 2 weeks between individuals at 
the same dose, and 3 weeks between dose groups. 
Although the final choice of dosing intervals will be determined by the data 
in part A defining the pharmacodynamics of expression of the vector-derived 
CFTR cDNA, it is most likely that the expression will wane in <90 days, and 
thus the dosing intervals for part C will be at 1, 90 and 180 days. In this 
context, the doses (each at 100 jxl volume) and time intervals for part C will 
be : 
[ 210 ] 
Recombinant DNA Research, Volume 20 
