to 7 day observation period. Of animals receiving vehicle followed by 
vehicle, (6/6) survived over the 3 to 7 day period, as did naive animals 
(6/6) , animals receiving vehicle alone (10/10) , and animals receiving 
vehicle followed by Ad5 (10/10). Studies with a larger group of animals 
(study CRCW.009) are ongoing to evaluate dosing and timing. 
Studies are also ongoing in rhesus with n-2 receiving AvlCFl (intra- 
bronchial 2xl0 10 pfu/kg) followed 1 week later with Ad5 ( intrabronchial 10* 
pfu/kg) (rhesus study 4C and 5C) . Controls include Ad5 alone (n-2), AvlCFl 
alone (n=2) and a naive animals (n-1) . All are alive and well 83 days after 
administration of the wild type Ad5 virus. All cultures for adenovirus in 
A549 and 293 cells are negative. Further, there have been no changes in 
clinical parameters detailed in Section 4.4. 
In regard to the environment, a series of studies have been carried out to 
demonstrate that shedding occurs infrequently, and only at early times 
after AvlCFl therapy. These studies are detailed in Section 4.7. In regard 
to the environment on the 7 West Clinical Center ward, the treated individ- 
uals will be maintained in rooms negative to the hallway (with HEPA filters 
for the exhaust) and under gown and glove respiratory precautions until 
documented to not be shedding virus (nasal, pharynx, rectal) on three sepa- 
rate days (see Section 5.6). 
All available evidence supports the concepts that: (a) shedding of an El - 
E3~ adenovirus vector will be minimal in amount and duration; (b) that 
under the circumstances of this protocol it is unlikely that a replication 
competent adenovirus will be derived from a vector of this design; and (c) 
that a virus that poses a danger to others will not be formed or released 
to the environment. However, until the studies are carried out in humans 
with cystic fibrosis, it is not possible to prove this with absolute cer- 
tainty. It is in this context that the study individuals are being asked 
that if they continue to shed virus (AdCFTR or an AdCFTR- derived virus) , 
they will be asked to stay on the 7 West patient care unit in the Clinical 
Center until the shedding has stopped. It is recognized that the physicians 
caring for the study individuals can only ask the study individuals to 
agree to these conditions, but cannot compel them from leaving the isola- 
tion conditions and the Clinical Center at any time they choose to do so. 
The one exception to this is in the extraordinary unlikely, but theoreti- 
cally possible, circumstance in which the physicians believed that, due to 
an untoward event, AdCFTR combined with another virus or other genetic 
information to create a new virus that was believed to be dangerous to 
others. In this situation NIH Clinical Center regulations allow the study 
individuals to be kept against his/her will for up to 72 hours. During that 
period, the physicians have the option to ask for a court order to keep the 
study individual confined until the risk to others is over. Although it is 
extremely unlikely for this to occur, because it is not possible to prove 
that it is impossible, this theoretical scenario is explicitly stated in 
the consent form (Section 5.13). 
4.10 Is There a Risk of Malignancy Associated With the Use of This Vector? 
There is no proven association of malignancy and adenovirus infection in 
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