Recombinant DNA Advisory Committee - 03/1-2/93 
Center. 
Dr. Whitsett stated that all patients will be followed long-term, and that an autopsy will 
be requested in the event of death. With regard to the number of x-rays that will be 
required, the number of x-rays will be greatly reduced because the second dose of vector 
will now be deleted. As the protocol was originally written, the proposed dosage of 
radiation was within the National Radiation Safety Council's Guidelines. The new 
dosimetry will be half of what was outlined in the original protocol. With regard to the 
ability to measure potential differences (PD), data was presented demonstrating a nasal 
PD of 80 millivolts in a CF patient as compared to 10-20 millivolts in normal individuals. 
Dr. Whitsett concluded that the investigators' intent is to formally remove the 
rechallenge portion of the protocol. The second dose protocol will be resubmitted to the 
RAC when the in vivo data is complete and the clinical efficacy of the initial trials has 
been evaluated. 
Committee Motion 
A motion was made by Dr. Haselkom and seconded by Dr. Motulsky to approve the 
protocol as amended to include a single administration of the adenovirus vector. 
Dr. Miller said that the RAC has always required that there be less than 1 adenovirus 
helper virus particle per patient dose; however, this requirement may be unnecessary. 
The problem is that there is no solid data with regard to the number of particles that 
will produce complications in a CF patient. Dr. Trapnell explained that CF patients are 
routinely exposed to adenovirus infections at the same rate as normal individuals, and 
both groups demonstrate similar clinical responses as demonstrated by gross examination. 
Ms. Grossman asked if the patients enrolled into this protocol will have be sicker than 
the average CF patient. Dr. Wilmott responded that the eligibility criteria includes 
patients who demonstrate mild to moderate disease. Initial patient accrual will include 
patients with mild disease. 
Dr. Parkman asked about the threshold dose to get a wild-type adenovirus infection. Dr. 
Whitsett answered that one-half of all individuals get a cold when exposed to 
concentrations of between 1 x 10 3 and 1 x 10 4 adenovirus particles. It is unknown how 
many adenovirus particles are transmitted in a human cough. Dr. Miller noted that 1 x 
10 3 particles is not an enormous dose; therefore, it is reasonable to allow this upper 
limit. 
Dr. Straus explained that the argument that CF patients have normal immunity to 
adenovirus is somewhat flawed, because all individuals acquire these infections at a 
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