Genzyme Corporation Ad2/CFTR-2 Gene Transfer Protocol: Single 
One Kendall Square, Cambridge, MA 02139 Aerosol Administration to the Lung of CF Patients 
years of age or older, e) Patients who are healthy enough to discontinue Pulmozyme aerosol and/or Tobramycin 
therapy for 4 weeks prior to Ad2/CFTR-2 treatment and not resume therapy for 4 weeks after they complete the study, 
f) Pregnancy: all subjects must adopt a reliable (greater than 90% effective) form of contraception for at least 1 month 
before the study, during the course of the study, and for 1 month following the last administration of Ad2/CFTR-2. g) 
Patients who are committed to follow the protocol requirements as evidenced by written informed consent. 
Exclusion Criteria 
a) Patients who have experienced an exacerbation of their disease requiring hospitalization within 3 weeks prior to 
Ad2/CFTR-2 treatment b) Patients who have had an upper respiratory infection (URI) within 2 weeks prior to 
Ad2/CFTR-2 treatment c) Patients who have evidence of adenoviral shedding within 3 weeks prior to Ad2/CFTR-2 
treatment, d) Patients with a confirmed positive culture of Pseudomonas cepacia or atypical mycobacteria within the 
last year, e) Patients who have hypoxemia (i.e. SaC >2 < 90%) f) Patients who have a FEVi < 40% of predicted g) 
Patients whose weight for height is < 25 % of predicted norm for their age. h) Patients who have been treated with 
systemic or aerosol steroids within 3 months prior to enrollment in the study, i) Patients with a known allergy to 
Xylocaine or Pontocaine or a bleeding diathesis, j) Patients who are pregnant or are unwilling to adopt a reliable form of 
contraception k) Patients living with children under the age of 6 years of age in their household. I) Patients with 
advanced liver, renal, cardiovascular or neurological disease who, in the opinion of the investigator, may not be healthy 
enough to successfully complete all protocol requirements or in whom results may be particularly difficult to assess, m) 
Patients with a serious active infectious disease and/or who have tested positive for either hepatitis-B surface antigen or 
HIV. n) Patients with a recent history of alcoholism or drug abuse (including tobacco), severe emotional, behavioral or 
psychiatric problems who, in the opinion of the investigator would not be able to adequately comply with the 
requirements of this study, o) Patients participating in another ongoing investigational drug study. 
Study Design 
This study is designed as a multicenter, single administration safety study. A total of 16 patients will be enrolled in the 
study. Two patients will be assigned to one of 8 groups. Each patient assigned to an individual group will receive the 
same dose of Ad2/CFTR-2. Each subsequent group is assigned to receive a one half log increase in the dose of 
Ad2/CFTR-2 as follows: 
Group 
IU 1 
MOI (Lung) 2 
MOI (Lobe) 3 * 
1 
8x10 6 
.002 
.013 
2 
2.5 xIO 7 
.007 
.042 
3 
8x10 7 
.023 
.13 
4 
2.5 xIO 8 
.066 
.42 
5 
8x10 8 
.23 
1.3 
6 
2.5 xIO 9 
.66 
4.2 
7 
8x10 9 
2.3 
13 
8 
2.5 xIO 10 
6.6 
42 
Patients will be enrolled and receive treatment in a staggered manner. Two patients in each group will receive aerosol 
administration of Ad2/CFTR-2. In our concurrent lobar study, three patients in each dose group (the dosing is the same 
for both studies) will have received lobar administration of Ad2/CFTR-2 via bronchoscopy. Following a 2 month 
monitoring period, and after 3 additional patients in the lobar study have received the next higher lobar dose, 
aerosolized treatment to the entire lung will begin on the first 2 patients in the first dose group in this study. This feature 
and the following intercalated staggered schedule provide additional safety in that the dose to be administered by 
1 This assumes the clinical lot will have a particle to IU ratio of 100/1 . 
^is assumes the target for aerosol administration is 4 x 10 9 airway cells. 
3 This assumes that 1 5% of the total airway is within the right middle lobe. 
Recombinant DNA Research, Volume 20 
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