exacerbations of respiratory infections and/or decrement in clinical lung- 
related parameters will occur during the baseline period, vehicle control 
period, or AdCFTR experimental treatment period. Further, the natural history 
of the disorder suggests it is possible that exacerbations of manifestations 
of the disease in other organs might also occur. 
Should intercurrent exacerbations of disease of any organ occur either during 
initial assessment or after therapy with the vector, the patients will be 
treated by conventional clinical therapy. During the period of intercurrent 
illness, assessment of safety and efficacy parameters will continue as defined 
by the protocol as long as such assessment does not interfere with the 
clinical care and welfare of the patient. 
If intercurrent illness occurs during the baseline period or vehicle control 
period, efforts will be made to determine if adenovirus is involved by nasal, 
pharynx, urine and rectal culture. If adenovirus is definitively shown to be 
involved, the individual will be removed from the protocol and not allowed to 
enter the AdCFTR experimental treatment period. 
If the intercurrent illness during the baseline or vehicle period control 
period is sufficiently severe to preclude continuation of the protocol, the 
individual will be removed from the protocol. 
If intercurrent illness occurs during the AdCFTR experimental treatment 
period, efforts will be directed toward determining whether the vector or 
replication competent adenovirus is involved, including viral culture of 
nasal, pharynx, urine and rectum and assessment of respiratory epithelial 
cells and inflammatory cells for the presence of AdCFTR or replication 
competent adenovirus DNA. If the intercurrent illness (independent of course) 
during this period is sufficiently severe to preclude further participation, 
the individual will be removed from the protocol, but will remain in the 
Clinical Center until proven not to be shedding adenovirus as dictated by the 
protocol (see section 5.6.4). 
If a study individual has to be removed from the protocol because of 
intercurrent illness, a new individual will be substituted to begin the 
protocol. Removal of an individual will be reported to the Institutional 
Clinical Research Subpanel (ICRS), NHLBI ; the Institutional Biosafety 
Committee (IBC) , the National Institutes of Health (NIH) ; the Recombinant DNA 
Advisory Committee (RAC); and the Food and Drug Administration (FDA). 
5.6.6 Management of Adverse Events 
Adverse reactions will be defined for each organ system based on a four grade 
scale (Table 5.6.6-A). If an adverse reaction occurs attributable to adminis- 
tration of the vector , the individual will be treated by conventional clinical 
therapy. Assessment of safety and efficacy parameters will continue as defined 
by the protocol as long as such assessment does not interfere with the 
clinical care and welfare of the patient. No additional patients will be 
treated until the data is discussed with the ICRS, NHLBI, IBC, NIH, and the 
FDA. The occurrence of the adverse reaction will be reported to the ICRS, IBC, 
RAC, and the FDA within 24 hours of its recognition. 
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Recombinant DNA Research, Volume 16 
