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 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 a study individual has to be removed from the protocol because of an 
adverse reaction unrelated to the AdCFTR vector, a new individual will be 
substituted to begin the protocol. This will be reported to the ICRS, NHLBI , 
IBC, NIH, RAC and the FDA. If the study individual has to be removed from the 
protocol because of an adverse relation related to the AdCFTR vector, a 
decision to add a substitute patient will be made only after discussion and 
agreement of the ICRS, NHLBI, IBC, NIH, 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 AdCFTR and replication competent Ad5 using PCR 
and viral cultures as outlined in the protocol. 
5.6.7 Ability of the Protocol to Answer the Questions Posed in the Intro- 
duction to the General Design (Section 5.1) 
As detailed in Section 5.1, the protocol is designed to answer six questions 
central to evaluating the use of a replication deficient, recombinant 
adenovirus containing the human CFTR cDNA to treat the respiratory manifes- 
tations of cystic fibrosis. The following details how the protocol design will 
answer these questions. Conclusions regarding the answer to each question will 
be made by statistical evaluation appropriate for each parameter. At a 
minimum, however, a formal data base will be established for all parameters 
measured . 
(1) Is it safe? The extensive general and adenovirus -related safety data 
will answer this question for a one time administration to the 
target organs as a function of increasing dose. 
(2) Will it provide biologic correction in respiratory epithelial cells? 
This question will be answered by assessing respiratory epithelial 
cells before and after therapy for a variety of biologic parameters 
relevant to expression of the CFTR gene. 
(3) Chronicity? If biologic correction is achieved, the protocol will 
define how long the correction will last in the target organ. 
(4) Respiratory epithelium electrical potential difference correction? 
Based on the knowledge that individuals with cystic fibrosis have an 
elevated potential difference between the epithelial surface and the 
subcutaneous tissues secondary to the primary genetic abnormality, 
the protocol will determine whether the therapy will correct the 
epithelium in vivo. 
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