The 2 individuals in each treatment group will be staggered by a minimum of 1 
week 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 no adenovirus can be detected in nasal, pharynx, blood, 
rectal or urine cultures on 3 separate days, the protocol will move to the 
group receiving the next dose level no earlier than 1 week 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 in Section 5.6.5. 
If an adverse event occurs during the therapy period, it will be managed as 
described in Section 5.6.6. 
The vector will be administered at the dosage and to the sites described in 
Section 5.6.1. The nasal administration will be carried out through a nasal 
speculum under direct vision to the inferior turbinate. The bronchial 
administration will be carried out slowly to a main stem bronchus via a 
fiberoptic bronchoscope. 
To minimize the risk from intercurrent infection (viral or other) during the 
initial phase after administration of the vector, the individual will be 
isolated (see above) for 10 days prior to being treated with the vector and 
will be clinically evaluated prior to administration of the vector to insure 
there is no intercurrent viral illness. Further, after administration of the 
vector, the patient will continue in isolation until demonstrated not to be 
shedding (nose, pharynx, urine, rectal) the vector or replication competent 
adenovirus on at least three different days. 
From the data available, it is very unlikely that shedding of AdCFTR will 
extend beyond a few days to a few weeks (see sections 4.1, 4.5, 4.7, 4.8, 
4.9). If the situation does arise that shedding continues, the patient 
receiving AdCFTR will remain in the Clinical Center under the conditions 
described in this section until shedding is no longer detected on 3 separate 
days. This mandatory criteria for participation in the protocol, with the 
caveats regarding the rights of the individual to leave, is described in the 
Informed Consent (see section 5.13). 
To insure protection of the environment, the patient rooms to be used on the 
Pulmonary Branch 7 West clinical unit, building 10 will be converted to be 
negative pressure to the corridor and filtered as approved by the Biosafety 
Office, NIH. 
After administration of the vector, the patient will be evaluated with the 
safety and efficacy parameters as detailed on the time line in Figure 5.6.4-A. 
5.6.5 Management of Intercurrent Illness 
The natural history of cystic fibrosis is associated with exacerbations of the 
disease, particularly the respiratory manifestations (Boat et al . , 1989). In 
this context, it is possible that among the 10 individuals in this protocol, 
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