Recombinant DNA Advisory Committee- 9/12-13/94 
back to school or work. He noted that it is not possible to obtain Informed Consent 
document from all the potential contacts. Dr. Flotte said that at time zero, right after 
vector administration, nasal fluids, bronchial fluids, urine and stool samples will be 
collected; and at day 3 and day 10 all samples except the bronchial fluid will be assayed 
for the presence of vector. At day 30 and day 60 patients will return for repeat 
bronchoscopy, and samples will be taken for vector assay. 
Dr. Straus did not believe one could fairly impose prolonged hospitalization. If patients 
test positive for vector shedding after 7 or 10 days, they will be sent home but no 
additional patients should be recruited until the biology of the vector is better understood. 
He would not favor keeping a patient indefinitely, nor could he approve a protocol that 
allows many people to go home shedding virus. 
Dr. Dronamraju questioned the adequacy of the monkey model in terms of social 
behavior. Dr. Parkman said the monkey model is adequate to address the duration of 
vector secretion. Patients will be isolated initially for 10 to 14 days to observe vector 
shedding either from the initial vector inoculum or due to vector replication. Differences 
in the behavioral pattern of monkeys and humans are not significant in this case. But if 
there is a long-term persistent secretion, then behavioral pattern will be a significant 
factor in the spread of the virus. Regarding Dr. Dronamraju’s question on the number of 
patients, Dr. Flotte said that 16 patients are required to test dose escalation with 2 
patients in each dose group. 
Regarding the question of virus shedding, Dr. D. Ginsburg suggested a study of 1 patient. 
If there is no long-term virus shedding in the first patient, RAC members may feel more 
comfortable in allowing treatment of additional patients. Dr. Flotte said that each cohort 
is separated by an interval of 1 month, and it is agreeable to report back to the RAC 
between each cohort. Dr. Straus said if long-term vector shedding is observed in the first 
cohort, no other cohort should be started. However, the patients should be allowed to go 
home. 
Mr. Capron said that the Informed Consent document should be revised to incorporate a 
statement that informs subjects that in the event they choose to withdraw from the study 
after the vector administration, they will be strongly discouraged from leaving the hospital 
until lack of virus shedding has been demonstrated. Although the patients still have the 
legal right to leave the hospital, they would be encouraged not to do so under such 
circumstances. Dr. Flotte agreed to modify the Informed Consent document to reflect this 
concern. Ms. Meyers said that the revised Informed Consent document should be 
reviewed by RAC primary reviewers. 
Regarding the question of transgene expression, Dr. Flotte made a slide presentation of a 
monkey study. In situ PCR was used to detect the AAV-CFTR sequences in bronchial 
epithelial cells after vector administration. At 3 dose levels up to 10 11 particles, 13 to 51% 
of epithelial cells were found to contain the vector DNA for up to a period of 21 to 90 
days. The result was very similar to a more thorough study in rabbits on the question of 
transgene expression. 
Recombinant DNA Research, Volume 20 
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