Recombinant DMA Advisory Committee - 12/2-3/93 
complete responses to the Points to Consider have been provided. The investigators 
propose to use a modified adenovirus vector construct for which safety and efficacy have 
been addressed in the preclinical animal studies. Several minor changes should be made 
to the Informed Consent document. Since this protocol is a Phase I/II study, the term 
"treatment" should be replaced with the word "procedure," and the term "gene therapy" 
should be replaced by "gene transfer." Patients should be informed that a determination 
will be made whether they are seropositive to adenovirus. Since this protocol is well 
presented and all of her original concerns have been adequately addressed, Dr. DeLeon 
recommended approval of this proposal. 
Review~Mr. Capron (presented by Dr. DeLeon) 
Dr. DeLeon summarized Mr. Capron's written review. The protocol was well-presented. 
Several minor issues concerning the vector construct have been adequately addressed by 
the investigators. The number of patients to be enrolled on this study is reasonable and 
will be limited to those individuals who are seropositive to adenovirus. This criterion 
will facilitate a rapid immune response and minimize risk of virus transmission. Two 
separate Informed Consent documents have been approved by the IRB, one document 
for the nasal epithelium study and another document for the maxillary sinus study. Both 
of these Informed Consent documents are complete, well presented, and understandable 
to laypersons. 
Other Comments 
Ms. Grossman said that the investigators have stated that there were several animal 
deaths in the preclinical studies. Why was the cause of death undetermined? The 
investigators need to provide an explanation as to why little differences were observed 
between single and multiple vector administration in the animal studies. Why was mild 
inflammation observed in animals at multiple high doses of vector? The RAC must 
decide whether an open ended vector modification should be approved for this study 
since significant changes in vectors may affect the immunological responses. The 
investigators should elaborate on their request to decrease the patient isolation period to 
24 hours. 
Dr. Post suggested that a reasonable compromise regarding the proposed vectors would 
be for the RAC to approve the use of the previously approved vector (AD2/CFTR-1) as 
well as the proposed vector (AD2-ORF6/PGK-CFTR). Any future vector modifications 
should be submitted as requests for minor modifications. 
Dr. Leventhal noted that the highest proposed dose, 10 10 cfu, is a higher dose of 
adenovirus than the dose that resulted in the adverse effect reported by Dr. Crystal. Dr. 
Parkman stated that the RAC may want to reconsider the proposed isolation period for 
the maxillary sinus administration arm of the study since the vector may persist for a 
longer period in this isolated area. Ms. Meyers stated that the Informed Consent 
document does not include recommendations for male contraception, period of 
contraception, long-term follow-up, and responsibility for costs associated with research- 
Recombinant DNA Research, Volume 18 
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