Revised 8-26-94 
Potential Risks : 
The potential risks of this protocol may be divided into two main types: (1) 
those associated with the various tests and procedures designed to show effec- 
tiveness and safety; and (2) those associated with administration of a repli- 
cation deficient adenovirus containing the normal CF gene to individuals with 
CF. 
To first consider the problems associated with the various tests and proce- 
dures in the protocol it should be noted that all the tests used are widely 
accepted tests in clinical medicine and in most instances would form an impor- 
tant part of your ongoing care. All these tests are monitored by regulatory 
bodies so that strict standards are upheld. These include limitations on the 
amount of blood which can be drawn and the amount of radiation you may be 
exposed to during the different parts of the protocol. Furthermore the inva- 
sive tests such as nasal instrumentation and bronchoscopy with its attendant 
procedures will all be performed by experts with much experience in these 
fields . 
Theoretically, there are several potential risks of giving AdcvCFTR.lO to in- 
dividuals with CF. Potential risks are from the specific adenovirus to be used 
in this protocol, and finally from the product of the genetically modified ad- 
enovirus to be used in this protocol. Adenoviruses are a common cause of re- 
spiratory problems in man, usually of a non-serious type, unless the infected 
individual has a poor defense against germs. The adenovirus used in this 
protocol has been modified so it will not grow in your tissues. Therefore 
infection with this adenovirus per se is not felt to pose a major problem. 
It is theoretically possible that the Ad^vCFTR-lO virus will combine in some 
way with another adenovirus and thus acquire the ability to reproduce itself. 
This might lead to increased production of AdcvCFTR.10 and an ongoing adeno- 
virus infection. Another possibility is that the AdcvCFTR.lO may acquire some 
genetic material from another adenovirus or other virus leading to the produc- 
tion of some form of mutant adenovirus. These potential problems would not 
only affect you but could also potentially affect other individuals. In order 
to prevent this from occurring this protocol has built into it certain safe- 
guards. First, if there is any evidence of adenovirus or other major respira- 
tory viral infection, you will not be included in the study. Therefore, any 
possible combining of AdcvCFTR.10 with other viruses will likely involve 
viruses acquired after starting the protocol. To minimize the chance of this 
occurring during the initial phase after administration of AdcvCFTR.10, you 
will not receive AdcvCFTR.10 if you have had a new respiratory infection 
within 1 week prior to treatment. To protect others, you will be isolated for 
2 days following each administration of Ad^vCFTR.lO. These problems, while 
theoretically possible, have never been seen in studies using AcIqvCFTR.IO in 
animals at dosages similar to those intended for use in humans. 
While it is theoretically possible that the material produced by the CFTR gene 
in AdcvCFTR.10 may be recognized as "foreign" by the immune system of the par- 
ticipant resulting in the immune system attacking the body, there is no 
evidence to suggest that this will happen and participants have been chosen to 
include only those who do produce a CFTR protein (even though it is an abnor- 
mal one) so that the normal protein is less likely to be entirely "foreign" to 
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