M.J. Welsh and A.E. Smith, RAC Application 
Ad2-ORF6/PGK-CFTR 
Item 5 - Clinical Protocol 
Measurement of Nasal Voltage, Measurement of Vt will not produce significant discomfort; it has 
generally been well tolerated in the past The drugs applied topically to the nasal epithelium during the 
course of the study have no significant local or systemic effects. 
Application of Ad2-0RF6/PGK-CF1 R. Application of the recombinant virus to the nasal mucosa should 
have no significant risk. There could be minor discomfort or a sense of nasal obstruction. There may 
also be discomfort from having to remain still during the procedure. These discomforts should be 
minimized by administration of Midazolam 1-2 mg. IV. shortly before application. The major risks of 
Midazolam would be hypersensitivity which is very rare. The Midazolam could theoretically produce 
some respiratory depression; however the dose we will use should have no significant effects, particularly 
in these subjects who will only have mild to moderately severe disease. 
Chest Computed Tomography Chest CT carries the risk of radiation exposure; we anticipate that a 
subject will have two chest CTs during the course of the study. Although there are no known adverse 
effects of this amount of radiation, the long term effects of such radiation are not known with certainty. 
Potential Benefits. 
It is very unlikely that participation will directly benefit the patient. The correction of the genetic defect of 
CF will likely be limited to the area of virus application in the nose for those patients enrolled in Part A 
and in the sinus for those patients enrolled in Part B. 
The primary benefit will be the information obtained from this study regarding the safety and efficacy of 
gene transfer by recombinant adenovirus. Such information is criucal for further development of gene 
transfer for CF lung disease. If this work is able to lead to the development of better treatments for CF, 
there will be a potentially large benefit to mankind. 
The overall risks to the patients appear to be small in view of the care taken to develop a viral/gene 
construct which is defective in replication and which, in wild-type form, is known to produce relatively 
mild disease. The risks are minimized by use of nasal mucosa. Given the potential benefits of the 
information to be gained by human trials, the risk appears to be justified. 
STUDY PLAN, PART B 
Study Design. 
This is a non-randomized, nonblinded administration of recombinant Ad2-ORF6/PGK-CFTR to the 
maxillary sinus epithelium. Athough administration of vector will not be blinded, the analysis of many 
of the results will be blinded, using the saline-treated contralateral maxillary sinus as a control. 
Number of Participants. 
We intend to study five to ten patients. All patients will be identified in the first year. Patients will be 
referred to the study for consideration their physicians. 
Selection Criteria. 
Inclusion Criteria 
The criteria are the same as the selection criteria in Part A with the following additional criterion: 
e) Maxillary sinus disease. Patients must have bilaterally opacified sinuses on sinus CT scan. 
Exclusion Criteria 
The criteria are the same as the exclusion criteria in Part A with the following additional criterion: 
m) Patients would be excluded from the study if the CT scan demonstrated sinuses that were so 
hypoplastic that there would be potential technical difficulties in their safe cannulation. The patient's nose 
would be endoscopically examined and those patients with massive polyposis or with severe septal 
deformities would be excluded. Those two factors would serve to prevent proper anatomical access to the 
maxillary sinus via the inferior meatus. 
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Recombinant DNA Research, Volume 18 
