M.J. Welsh and A.E. Smith, RAC Application 
Ad2-ORF6/PGK-CFTR 
Item 5 - Clinical Protocol 
STUDY PLAN, PART A 
Recombinant Adenovirus Direc ting Expression of Human CFTR. 
The recombinant adenoviral vector/CFTR gene construct, Ad2-ORF6/PGK-CFTR, will be made at 
Genzyme Corporation, Framingham, MA. It will be tested at Genzyme Corporation and at outside 
contractors, including Microbiological Associates, Bethesda, MD. 
Study Design. 
This is a non-randomized, non-blinded administration of recombinant Ad2-ORF6/PGK-CFTR to 
respiratory nasal epithelium. Although administration of vector will not be blinded, the analysis of many 
of die results will be blinded, using the saline-treated contralateral nasal mucosa 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 by their physicians. 
Selection Criteria. 
Inclusion Criteria 
a) Patients with CF with mild to moderate severity of disease. Patients should score above 70 using the 
CF NIH scoring system (39). 
b) Male or female patients, age greater than 1 8 years. 
c) CF genotype: AF508 homozygous is preferred. If patients homozygous for AF508 are not available, 
we will treat patients with other defined genotypes known to be associated with CF. 
d) Seropositive for antibody to adenovirus. Seropositivity is very common (greater than 70%) in the 
general population (40). Seropositivity is required to insure a rapid and adequate immunologic 
response to the virus and to minimize any potential for dissemination of the virus. 
e) We will not exclude subjects who have participated in our first gene transfer protocol involving a one 
time, low dose administration of Ad2/CFTR-1. 
Exclusion Criteria 
a) Current instability of respiratory status. 
b) Hypoxemia with P a 02 less than 70 mm Hg. 
c) FEV l less than 50 % of predicted. 
d) Weight for height (%) less than 75 % of predicted. 
e) Pregnancy: all subjects must practice contraception for at least one month before the study and then 
during the course of the study. Women must have a negative test for pregnancy. 
f) Patient has school age children. 
g) Chronic severe nasal/sinus disease, either infectious or allergic in nature. Persistent purulent nasal 
discharge, obstructing nasal polyps, significantly inflamed nasal mucosa, or symptomatic sinusitis 
requiring repeated antibiotic therapy will exclude patients from the study. 
h) Upper respiratory infection of patient or household member within two weeks prior to entry. 
i) Chronic adenoviral shedding within three weeks of study as detected in blood, urine, and nasal 
swabs. 
j) Patients with a known allergy to Xylocaine or Pontocaine or a bleeding diathesis. 
k) Subjects may not participate in other research protocols during the proposed study. 
l) Inability to comprehend nature of the study or to give informed consent. 
Timing of Evaluations. 
To insure clinical stability, participants will enter the study at least 3 weeks before administration of virus. 
They will then be evaluated at the times indicated on the attached flow sheet The specific evaluations are 
listed below. It is possible that the first pretreatment evaluation could be longer than three weeks before 
Ad2-ORF6/PGK-CFTR administration. At the discretion of the investigators participants may also 
receive any of the evaluations between enrollment and administration of the recombinant virus if there is a 
significant change in clinical status. 
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Recombinant DNA Research, Volume 18 
