be administered at the dosage and to the sites described above. 
7. Part B. Part B is designed to evaluate the safety of repeat administration 
at the same dose, and whether expression can be achieved with repeat admini- 
stration, and if so, how much at which level. Repeat dosing will be initiated 
at a dose and time interval to be determined by the observations in Part A. 
Three groups of individuals will be studied in part B, with n=4 in each group 
(i.e., for a total of 12 individuals). The requirement of 4 patients/group is 
justified by the need to insure reproducibility of the repeat dose efficacy. 
7.1 Baseline Period/Part B. Identical to baseline in Part A 
7.2 Vehicle Control Period/Part B. Identical to baseline in Part A 
7.3 AdoyCFTR.lO Treatment Period/Part B. The first group of naive patients 
will be started in group B at the first dose level used in part A that safely 
demonstrated expression was observed in part A (at a minimum) at day 4 and/or 
14 after administration with 2 patients at the same dose. The interval of 
dosing will be determined by the pharmacodynamic expression data in part A, 
but the dosing interval will not be more frequent than every 30 days. The 
entire dosing period will not be for more than 180 days. The dose for the 
first group of individuals in part B will be chosen by the criteria detailed 
above. The second and third groups in part B will have doses 1 log and 2 logs 
higher, respectively. However, patients will be entered into these second and 
third groups only if the doses to be used have already been evaluated in part 
A and the expression criteria detailed above are met. As an example, assume 
that in part A, expression is not observed at day 4 and/or 14 in either 
patient at a dose of 10 s pfu and in only 1 of 2 patients at day 4 and/or 14 at 
10 s 5 pfu, but in both patients at day 4 and/or 14 at the 10 7 pfu dose. These 2 
patients (i.e., the 10 7 pfu dose) are followed and expression is no longer 
observed at day 30 or 60. Part A will continue at higher doses, but the obser- 
vation of the 2 patients meeting the expression criteria at a dose of 10 7 pfu 
will trigger the start of part B. Four patients are then entered into part B 
at a dose of 10 7 pfu. Because expression was observed at days 4 and 14, but 
not at day 30, the repeat dosing schedule will be every 30 days for a maximum 
of 180 days (i.e., all 4 patients will receive 10 7 pfu at 3 sites at days 1, 
30, 60, 90, 120 and 150). 
Assuming that the expression criteria are met for both patients in part A at 
doses 10 8 pfu and 10 9 pfu, and the same pattern of expression at days 4 and 
14, but not at 30 and 60, then the second group in part B will be 4 patients 
receiving 10 8 pfu q 30 days (i.e., 1, 30, 60, 120 and 150), and the third 
group in part B will be 4 patients receiving 10 9 pfu q 30 days (same inter- 
vals). The interval between starting individuals in part B will be 2 weeks 
between individuals at the same dose, and 3 weeks between dose groups. 
Since the dose and interval between doses for each individual in part B will 
be determined in part A, it is not possible to detail the exact doses and in- 
tervals. However, as an example, assume the doses will be 10 7 , 10 e and 10 9 pfu, 
and the interval will be 30 days between doses. The 3 groups in part B will 
then receive repeat administration of the vector as follows (doses in pfu; 
each dose to be delivered in 100 jil) . 
Recombinant DNA Research, Volume 20 
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