5.1 PURPOSE OF THE STUDY: The purpose of this study is to evaluate the safety and 
efficacy of gene therapy in cystic fibrosis (CF) utilizing a recombinant adenovirus that is made 
replication deficient by deletion of the El region. Recombinant adenovirus (AVjCFj) will be 
used to deliver the human cystic fibrosis transport regulator (CFTR) cDNA to the upper and 
lower respiratory tracts of cystic fibrosis patients. 
Primary Objectives: 
1. To establish that adenoviral vector (AvlCF2)-mediated expression of normal CFTR 
can be achieved in the nose and lower respiratory tract of cystic fibrosis patients. 
2. To establish that expression of the AvlCF2-derived normal CFTR cDNA in the nose 
and lower respiratory tract of CF patients results in correction of transepithelial 
potential difference and restores cAMP-dependent chloride conductance. 
3. To determine the dose response and longevity of AvlCF2-derived CFTR expression 
after transfer of the normal human CFTR cDNA to the nasal and lower respiratory 
tract. 
4. To evaluate the safety of recombinant adenovirus (AvlCF2) therapy in patients with 
cystic fibrosis. 
5. To evaluate the antibody response to the recombinant adenovirus (AvlCF2). 
6. To determine whether expression of the CFTR gene in the lower respiratory tract of 
CF patients lends to improvement in mucociliary clearance in the treated lobe. 
7. To establish the effectiveness and safety of a single repeated administration of AvlCF2 
to thelower respiratory tract in CF patients. 
Secondary Objectives: 
1. To characterize potential toxicity to the lower respiratory tract, after in vivo AvlCF2 
infection, by assessing pulmonary function (measured by FEy^, radiographic 
abnormalities, and lung functions by perfusion scans and mucociliary clearance scans 
in patients receiving AvlCF2. 
2. To characterize the time course of viral survival and/or replication after AvlCF2 
treatment. 
5.2 RESEARCH PLAN: 
5.2.1 Subjects 
1. Three distinct groups of five patients each will be studied according to the clinical 
protocol, increasing the lung dose from 10 10 PFU to 10 u PFU and 10 12 PFU in a 
sequential manner, proceeding with each higher dose group after acute toxicity studies 
verify the safety of the regimen. Clinical toxicity of significance at any dose will 
obviate proceeding with increasing doses. The nasal dose will be 1 /200th of the lung 
dose based on surface area considerations. 
2. Cystic fibrosis patients > 18 years old will be eligible. 
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