Recombinant DNA Advisory Committee - 03/1-2/93 
1 replication-competent particle. Dr. Haselkom asked if the current PCR amplification 
utilizes a nested procedure with multiple rounds of amplification. Dr. Trapnell explained 
that the investigators are in the process of optimizing the nested procedure, and that this 
method should increase the level of sensitivity. 
Dr. Leventhal suggested that if the number of infectious particles is a real concern that 
the response of the initial 3 groups of patients can be used to evaluate toxicity. A 
stopping rule for toxicity should be based on the criteria that have already been 
developed. This study will provide valuable data about the number of infectious 
particles a CF patient can tolerate. Dr. Parkman responded that a direct correlation 
cannot be made since the actual number of infectious particles cannot be quantitated. 
Dr. Leventhal said that the committee should be confident that the experimental design 
of this protocol will not produce any extreme adverse reactions such as anaphylaxis. 
Dr. Parkman moved the question. The motion to approve the protocol is contingent on 
the following stipulation: (1) that the second administration of the adenovirus vector, 
AdlCF2, and associate clinical procedures will be eliminated from the protocol and the 
informed consent document. The RAC recommends that the investigators attempt to 
obtain a level of sensitivity adequate to detect 1 replication-competent virus particle per 
patient dose. The protocol was approved by a vote of 16 in favor, 0 opposed, and 2 
abstentions. 
XIII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: GENE TRANSFER FOR CYSTIC 
FIBROSIS USING El DELETED ADENOVIRUS: A PHASE I TRIAL IN THE NASAL 
CAVITY /DRS. BOUCHER AND KNOWLES 
Review-Dr. Post 
Dr. Walters called on Dr. Post to present his primary review of the protocol submitted 
by Drs. Richard C. Boucher and Michael R. Knowles of the University of North 
Carolina, Chapel Hill, North Carolina. 
Dr. Post explained that this protocol involves the intranasal administration of an 
adenovirus vector containing the gene coding for CFTR. The advantages of nasal versus 
lung administration is that the epithelium is easily accessible for biopsies and 
electrochemical analyses. 
This protocol will use the same adenovirus vector that was approved for Dr. Wilson's CF 
protocol at the December 1992 RAC meeting. Dr. Wilson, a co-investigator on this 
study, and will supply the vector. This vector has a cytomegalovirus (CMV)-enhanced p- 
actin promoter with an SV40 polyadenylation signals inserted into the El region. One 
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