Revised 8-26-94 
treat CF by delivering the normal gene to the cells lining the trach- 
eobronchial tree. How can the normal gene be delivered to these cells? The 
delivery system in this protocol involves placing the normal CFTR gene into 
AdcvCFTR.lO, a virus that has been modified in the laboratory, that can infect 
cells in the lung like a "cold" virus but cannot reproduce itself in human 
lung airway cells. In this fashion, AdcvCFTR.lO will be used like a shuttle to 
"ferry" the normal gene to the lung cells, thus compensating for the lack of 
normal CFTR genes. AdcvCFTR.10 will be administered to the respiratory tract 
of individuals with CF at three sites in the airways. Administration to the 
airways will be through a bronchoscope which is a flexible tube that can, with 
appropriate sedation and anesthesia, be placed via the nose or mouth into the 
lung. AdcvCFTR.10 will be placed in a small amount of fluid known as a 
vehicle. This vehicle is composed of a dilute mixture of salts and buffered 
glycerol which is a basic component of many natural fats in the body. It 
ensures that the virus remains functional. The actual volumes of material to 
be administered are 100 microliters (about 2 drops) to each of 3 sites in the 
airways. These volumes will not be uncomfortable for the patient. This 
procedure will be repeated on a schedule described later in this document. The 
protocol is designed to determine: (1) Is it safe to administer the modified 
adenovirus, AdcvCFTR.10, to the airways of individuals with CF? ; (2) Will 
transfer of the normal CFTR gene to respiratory epithelial cells of in- 
dividuals with CF enable these cells to produce the products of a normal, 
functional CFTR gene? Ultimately, the question is: will this strategy normal- 
ize that part of the lung to which the normal gene has been transferred?; (3) 
How long will this effect last?; and (4) can the transfer be repeated such 
that the correction in the airway cells is maintained? In this regard, does 
the body develop immunity against AdcvCFTR.lO that will prevent subsequent ad- 
ministrations, i.e., will the body react against the modified virus to prevent 
it from transferring the normal gene to the lung upon repeat administrations? 
Inclusion and Exclusion Requirements: 
Based on the natural course of cystic fibrosis and the need to maximize safety 
while at the same time perform various tests to evaluate the effectiveness of 
the treatment, the following inclusion and exclusion requirements for the 
study population have been defined. These requirements will be determined, to 
the extent possible, before entry into the protocol; some, however, will not 
be measurable until the baseline evaluation part of the protocol (see section 
6 in the protocol). It is possible, therefore, that although started, at some 
point you will not be able to continue in the protocol if you do not meet 
these requirements. Likewise, there are possibilities as part of the natural 
history of your disease (i.e., unrelated to the protocol itself) of your be- 
coming ill during the protocol. In such circumstances you may not be able to 
receive treatment with AdcvCFTR.10 or to continue with the protocol. These 
possibilities and how they will be handled are discussed in section 6 of the 
protocol . 
Inclusion requirements: 
You must be capable of providing informed consent. 
You must have cystic fibrosis as defined by routine clinical requirements 
(cough, abundant sputum production, recurrent lung infections, etc.). You must 
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