Che first group will be 3xl0 6 pfu) . To minimize the risk from spread of the 
vector, the patient will be in isolation for 2 days after administration of 
the vector to the lung. After administration of the vector, the patient will 
be evaluated with the safety and efficacy parameters as detailed in the time 
line in Appendix A5 . 3 . For part A, the intervals between starting new patients 
will be 2 weeks between patients at the same dose, 3 weeks between patients at 
new doses. The 7 groups in part A will receive a single administration of the 
vector as follows (doses in pfu; each dose to be delivered in 100 /il) . 
Patient # 
Dose at 
each 
site 
(pfu) 
# of sites of 
administration 
Sites 
Total dose to 
be administered 
to each patient 
(pfu) 
1A, IB 
lxlO 6 
3 
Each site in 
same lung, each 
just distal to 
lobar bronchi 
3xl0 6 
2A, 2B 
lxlO 6 5 
3 
Same 
3xl0 6S 
3A, 3B 
lxlO 7 
3 
Same 
3xl0 7 
4A , 4B 
lxl0 7S 
3 
Same 
3xl0 7S 
5A, 5B 
lxlO 8 
3 
Same 
3xl0 8 
6A, 6B 
lxlO 85 
3 
Same 
3xl0 8S 
7A, 7B 
lxlO 9 
3 
Same 
3xl0 9 
For each site, the estimated surface area that will be exposed to the vector 
is 4 cm 2 , to yield estimated multiplicity of infections (MOI) of 0.25 to 250 
(assuming each cell has an apical surface area of 10/im x 10/im) . Following ad- 
ministration of the vector the vector on day 1, the individual will undergo 
fiberoptic bronchoscopy on several occasions to evaluate Ad^CFTR. 10 -directed 
expression of CFTR until expression is no longer observed in two successive 
evaluations. Details of the time intervals to be used are in the time line, 
Appendix A5 . 3 . 
The individual will enter the treatment period within 2 months after complet- 
ing the vehicle control period. Prior to the administration of the vector, 
there will be a reassessment of all parameters (except for the CT scan) if 
the vehicle control period was greater than 2 months. The individual will then 
be ready for administration of the vector on day 1 of the treatment period. 
The 2 individuals in each treatment group will be staggered by a minimum of 2 
weeks to insure that no serious acute adverse reactions have occurred at the 
dose level for that group. Assuming no adverse effects in either individual of 
the treated group and nasal, pharynx, blood, rectal or urine cultures are neg- 
ative for each individual on 3 separate days, the protocol will move to the 
group receiving the next dose level no earlier than 3 weeks after the second 
individual (at the previous dose level) is treated. A similar pattern will be 
followed for each group. If an intercurrent illness occurs during the therapy 
period, it will be managed as described above. If an adverse event occurs dur- 
ing the therapy period, it will be managed as described above. The vector wil 1 
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Recombinant DNA Research, Volume 20 
