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 inflamma- 
tory cells for the presence of AdcvCFTR.10 or replication competent adenovi- 
rus DNA. If the intercurrent illness (independent of course) during this peri- 
od is sufficiently severe to preclude further participation, the individual 
will be removed from the protocol. 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 Review Board (IRB); the Institutional Biosafety Committee 
(IBC) ; the Recombinant DNA Advisory Committee (RAC); and the Food and Drug 
Administration (FDA) . 
9.2 Management of Adverse Events. Adverse reactions will be defined for each 
organ system based on a five point scale (see Appendix A6). If, in the judge- 
ment of the physician caring for the patient, an adverse reaction occurs 
attributable to administration 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 IRB, IBC, RAC 
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. If an adverse 
event occurs in response to the obtaining of safety and efficacy parameters 
unrelated to the vector itself, the assessment of safety and efficacy parame- 
ters 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 a study 
individual has to be removed from the protocol because of an adverse reaction 
unrelated to the AdovCFTR.10 vector, a new individual will be substituted to 
begin the protocol. This will be reported to the IRB, IBC, RAC and the FDA. If 
the study individual has to be removed from the protocol because of an adverse 
reaction related to the AdcvCFTR.10 vector, a decision to add a substitute 
patient will be made only after discussion and agreement of the IRB, IBC, RAC, 
and the FDA. Should the patient die while in this protocol, the family will be 
asked to give permission for a full autopsy to determine the precise cause of 
death (see Consent form) . Samples of all tissues obtained at autopsy will be 
evaluated for the presence of AcIqvCFTR.IO and replication competent Ad5 using 
PCR and viral cultures as outlined in the protocol. In the design of this 
protocol it is recognized that with the limited number of individuals to be 
studied and/or the doses used for only n-2 at each dose, that no biologic 
efficacy may be detected. If no biologic efficacy is detected and there are no 
safety problems associated with the AdCFTR vector, the approving committees 
will be asked to allow the number of study individuals to be increased. 
9.3 Health Care Workers. During the baseline and vehicle control periods, 
there are no additional safety issues for health care workers beyond those for 
usual clinical procedures for the evaluation and care of individuals with 
cystic fibrosis. During the AdovCFTR.10 therapy period, the health care work- 
ers will be exposed to no additional safety concerns beyond those for dealing 
with patients with infectious virus infection that can be spread by the respi- 
ratory and/or oral -fecal routes. Recommendations of the Institutional Biosafe- 
ty Officers will be followed for handling patients, biologic materials, bed- 
ding, towels, etc. Appropriate training sessions developed by the Investiga- 
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