• No evidence of cardiac, renal, central nervous system, major psychiatric 
disorders, musculoskeletal disease or immunodeficiency disease (includ- 
ing evidence of human immunodeficiency virus infection) . 
5. Safety and Biologic Efficacy Parameters. The study individuals will be 
monitored with a variety of safety, biologic and efficacy parameters during 
the control and Ad^vCFTR.10 treatment periods. The safety parameters are di- 
vided into two categories, "general clinical safety parameters" to monitor the 
individual's overall status as well as specific organ systems, and "vector- 
specific parameters" relevant to the administration of a replication deficient 
recombinant adenovirus. The biologic efficacy parameters are divided into 
"primary" and "secondary" as detailed below. The definitions for all parame- 
ters (including the list of all tests included under each parameter can be 
found in Appendix A3. The times of assessment for each parameter are detailed 
in sections 6-8. 
5.1 Safety parameters. The general clinical safety parameters include: general 
clinical assessment, general blood (CBC, ESR, clotting, chemistry, auto- im- 
munity, general immunity, culture, HIV, future), urine (routine, culture), 
EKG, roentgenographic (chest x-ray, chest CT) , lung function (routine, ABG) , 
sputum culture, bronchoalveolar lavage (cell number, type, culture, volume of 
epithelial lining fluid, inflammatory mediators), nasal brush (cell number, 
type) , bronchial biopsy (histology) . The vector related safety parameters in- 
clude: anti -Ad antibodies, anti -Ad cellular immunity, adenovirus culture (na- 
sal, pharyngeal, rectal, blood, urine), adenovirus DNA (nasal brush, bronchial 
brush), and serum (for inflammatory mediators). The total maximum radiation 
exposure for the roentgenographic parameters for each year of the protocol is 
within the amount judged safe by The Rockefeller University Hospital and NIH 
guidelines (less than 5 rads per year) . 
5.2 Efficacy Parameters. The primary biologic efficacy parameter will be quan- 
titative PCR evaluation of Ad^CFTR. 10 -directed mRNA expression in bronchial 
epithelial brush samples. Secondary efficacy parameters (all as optional mea- 
surements depending on the amount of biologic materials available and the 
standardization of the assays) include: bronchial brush CFTR protein by immun- 
ohistochemistry , CFTR function by halide efflux, bronchial biopsy AdcvCFTR.10- 
directed mRNA expression by PCR, CFTR protein by immunohistochemistry , and 
bronchial potential difference. 
The focus of these parameters is to demonstrate that the recombinant vector 
will compensate for the endogenous abnormal CFTR genes to provide normal CFTR 
gene-related expression to respiratory epithelial cells. The primary efficacy 
parameter will be evaluated in bronchial airway epithelial cells obtained by 
brushing the epithelium. The epithelial cells will be recovered periodically 
during the control period and during the AdcvCFTR.lO treatment period. The 
times of assessment of each parameter are detailed in sections 6-8. 
The use of secondary efficacy parameters will depend on the availability of 
biologic materials and the standardization of the assays. The CFTR protein 
assay by immunohistochemistry will be carried out as previously described 
(59). The CFTR-related function of the intact respiratory epithelial sheet 
will be evaluated by quantifying the potential difference between the surface 
of the airway epithelial and the subcutaneous tissues. In normal individuals 
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Recombinant DNA Research, Volume 20 
