Genzyme Corporation Ad2/CFTR-2 Gene Transfer Protocol: Single 
One Kendall Square, Cambridge, MA 02139 Aerosol Administration to the Lung of CF Patients 
disease will require repeat administration. Furthermore, the use and further development of adenoviral vectors will 
require demonstration of safety and clinical efficacy in CF lung airway epithelia involved by the disease. 
Therefore, Genzyme has decided to initiate clinical studies to examine the safety of a single administration of 
Ad2/CFTR-2 to the lung. Genzyme feels justified in taking this step because there was no evidence of viral replication 
or virus associated adverse effects, even at the highest doses tested, with the Ad2/CFTR-1 vector which we have 
administered to the nasal epithelium in the clinic. Furthermore, the doses of Ad2/CFTR-2 aerosolized to the lung will 
have been previously administered by bronchoscope to a lobe of the lung. 
To proceed safely and slowly, we have staggered the administration of each aerosolized dose being evaluated in the 
study with the doses of the concurrent lobar protocol. Each study dose will first have been administered locally to a lobe 
via bronchoscopy. Only after a 2 month observation indicates that it is safe to treat additional patients, will this study 
proceed with aerosolized administration of this same dose to the lung. The first 2 doses (8 x 10 6 and 2.5 x 10 7 IU) will 
be administered via bronchoscopy before proceeding with aerosol delivery of the first dose. 
By the time the first patient in this study will receive Ad2/CFTR-2 aerosolized to the lung, we anticipate that we will have 
obtained the following clinical safety data on Ad2/CFTR-2: 1) At least 4 patients will have received 2-5 doses of 
Ad2/CFTR-2 in the nasal portion of our nasal/sinus protocol, 2) At least 2 patients will have received dose levels of up 
to 1 x 10 10 IU, and 3) Clinical safety data on repeat Ad2/CFTR-2 administration to the maxillary sinus may be available 
and 4) Lobar administration of a comparable dose and the next higher dose will have been evaluated for safety. 
As illustrated below the MOI (infectious units per cell) range will be lower in this study than in previous studies: 
Protocol 
Vector 
Description 
Target Cells 
MOI Range 
CF93-0101 
Ad2/CFTR-1 
Single Administration Nasal 
2 x 10 6 
1-25 
CF93-1 101 A 
Ad2/CFTR-2 
Repeat Administration Nasal 
2 x 1 0 7 
1-500 
CF93-1 101 B 
Ad2/CFTR-2 
Repeat Administration Sinus 
1 xIO 8 
5-25 
CF94-0401 
Ad2/CFTR-2 
Single Administration Lobar 
6x10 s 
.013-42 
CF94-1001 
Ad2/CFTR-2 
Single Aerosol Administration 
4 x 10 9 
.002 - 6.6 
Thus, on an MOI basis, the dose administrations in this study are in the range of MOI levels which have been used 
safely in our studies. 
To monitor patients closely for a respiratory inflammatory response, each patient will undergo bronchoscopy 7 days 
after Ad2/CFTR-2 treatment, or sooner if clinically indicated, to examine the Ad2/CFTR-2-treated sections of the lung. 
Specimens from the brushing will be evaluated for gene expression by RNA template-specific PCR (RS-PCR). 
Bronchoalveolar lavage will have been performed in the concurrent lobar protocol as well. 
PATIENT POPULATION 
Adult patients with mild to moderate CF (NIH Score > 60) will be enrolled in this study. Prior to enrollment, the patient's 
pulmonary function will be at least 90% of their historical peak over the previous 12 months. Each patient will be 
clinically stable before administration of Ad2/CFTR-2. Specifically, they will not have had a CF exacerbation requiring 
hospitalization or evidence of adenoviral shedding for 3 weeks prior to treatment. Patients will also not have had an 
upper respiratory infection for 2 weeks prior to treatment. Patients who have participated in previous Ad2/CFTR-1 or 
Ad2/CFTR-2 clinical studies are eligible to take part in this study and in future studies. 
Inclusion Criteria 
a) Patients with a confirmed diagnosis of CF (i.e. CF genotype or 2 positive sweat tests and a clinical status consistent 
with CF); b) Patients with cystic fibrosis of mild to moderate severity (NIH Score > 60) c) Patients who are at least 90% 
of their peak in pulmonary function achieved within the last 12 months d) Male and female patients who are eighteen 
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Recombinant DNA Research, Volume 20 
