Genzyme Corporation Ad2/CFTR-2 Gene Transfer Protocol: Single 
One Kendall Square, Cambridge, MA 02139 Aerosol Administration to the Lung of CF Patients 
aerosol will have been observed after local (lobar) administration for 2 months and the next higher dose will also have ’ 
been administered to a lobe and observed for 1 month before the actual aerosol administration. 
The study will also collect data on the biochemical efficacy of administering aerosolized Ad2/CFTR-2 to the lung. A 
brushing will be performed 7 days after Ad2/CFTR-2 administration. Specimens from the brushing will be evaluated for 
biochemical efficacy (i.e. gene expression via RS-PCR). 
On page 17 there is a protocol flow sheet that sequentially outlines the two study designs and the timing of each dosing 
group. 
Serious Adverse Event Stopping Rule 
In the event that 2 patients develop WHO grade 3 toxicity or if any single patient develops grade 4 toxicity at any given 
dose in either of the concurrent long studies, further treatment at that dose or higher will be stopped until such time as 
we have evaluated and discussed the adverse events with the Food and Drug Administration. 
Study Duration 
It is anticipated that the study will take approximately 10 months to complete. 
STUDY PROCEDURES 
Pretreatment Phase : To insure patient eligibility and clinical stability, participants will enter the study and undergo the 
first pretreatment evaluation at least 3 weeks prior to treatment with Ad2/Cn"R-2. They will then be evaluated at the 
times indicated on the protocol schematic (shown on page 18). 
At the discretion of the investigators, participants may also receive evaluations in addition to those described below 
between enrollment and treatment of Ad2/CFTR-2 if there is a significant change in clinical status. These evaluations 
will consist of those specified for Pretreatment Evaluation for Day *7. 
At a minimum, the patients will be clinically stable prior to Ad2/CFTR-2 treatment as defined in the study eligibility 
criteria. 
Hospital staff dealing with study patients will not have active respiratory disease. 
i 
Aerosol Administration of Ad2/CFTR-2 : Aerosolized administration of Ad2/CFTR-2 will be performed utilizing a closed, 
jet nebulizer system. Ad2/CFTR-2 will be delivered under a hood, or in some other controlled environment to minimize 
the escape of any aerosolized particles. Decontamination of the room where the virus is administered will also be 
utilized between patient exposures to minimize the risk of cross contamination of patients from infectious agents which 
patients have been exposed to. i 
Genzyme has evaluated 4 commercially available nebulizer systems to be used in the clinical study. These 
experiments investigated the particle size distribution of various test particle concentrations. The objective is to 
maximize the generation of particles in the 1-3 micron size range. This sized particle is felt to be the optimal size for 
delivery to the airway epithelia. These experiments also evaluated the effect of different aerosol flow rates. The effect 
different systems have on viral inactivation rate from the impact against the baffle of the system is being investigated 
and will be available for calculation of dose prior to the initiation of this study. Based on results to date we will probably 
recommend using the Vortran MINIheart system. 
Post Treatment Procedures : During the post treatment monitoring phase, at the discretion of the investigator when 
clinically indicated, additional evaluations to those specified in the flow sheet such as full physical exams, complete 
pulmonary function tests, bacterial cultures and cytology may be conducted during the patient's stay in the hospital or at 
a patient visit. 
If the patient experiences a significant increase in respiratory symptoms (i.e. coughing, wheezing, dyspnea, hemoptysis 
and/or hypoxia, develops a fever or has evidence of leucocytosis) a chest X ray may be performed. If there is the 
Recombinant DNA Research, Volume 20 
[556] 
