Recombinant DNA Advisory Committee - 12/1-2/94 
approximately 1 hour to minimize the possibility of exhaling virus particles into the environment. Following 
release from the canopy, the subject will be required to remain in the negative pressure facility for 24 hours. 
Dr. Dorkin stated that the subjects will be monitored for viral shedding by culture conducted 24-hours post- 
vector administration. Culture results will be available at 3 days; if the culture results are negative, the subject 
will be discharged. If the culture results are positive, the subject will be required to remain in isolation until 
viral shedding is no longer detected. 
Dr. Parkman stated that the stipulations for approval of Dr. Flotte’s (#9409-083) adeno-assodated virus-CFTR 
protocol should be applied to this study. The following stipulations should apply: (1) Submit a revised 
protocol that explains that each cohort will be evaluated for virus shedding. If virus shedding is detected at 2> 
10 days post-vector administration, vector administration to subsequent cohorts is prohibited. Any subject in 
whom virus shedding has been detected 2 10 days post-vector administration will be released from the 
hospital; however, family members and close contacts will be informed of the possibility that the subject may 
be secreting virus. The RAC recommended that if a subject is released from the hospital while actively 
shedding vims, family members and dose contacts should be evaluated for the presence of the vector. Dr. 
Dorkin agreed to revise the protocol according to Dr. Parkman’s suggestions. 
Dr. Dorkin stated that Dr. Zallen’s request for an autopsy is in the revised Informed Consent document. Dr. 
Dorkin stated that complications unrelated to gene therapy, e.g., small bowel obstruction (a common 
complication of CF patients) will be covered by third-party insurance. Medical care will be provided for other 
complications (such as respiratory infection) for 3 months following treatment. Genzyme will not indemnify 
complications that occur after that 3 month period. Mr. Capron stated that such a policy is acceptable 
provided that these provisions have been dearly disclosed to subjects who are considering partidpation in the 
study. Dr. Dorkin agreed to clarify this issue in the Informed Consent document. 
Dr. Dorkin explained that decisions regarding patient accrual will be discussed weekly at the CF center and 
will involve all the members of the center who are involved in the care of patients. Accrual will not be based 
on a single physician’s recommendations. Dr. Zallen stated that it is preferable that a neutral person obtains 
Informed Consent. Dr. Dorkin asked if it would be acceptable to have the patient’s primary care physidan or 
another physidan at the center, other than the patient’s prindpal consultant, to obtain the informed consent. 
Dr. Zallen said that Dr. Dorkin’s suggestion is an acceptable arrangement. Dr. Lapey noted that the 
Massachusetts General Hospital IRB requires that a patient advocate obtain Informed Consent. 
Dr. Parkman suggested that health care workers should be required to provide Informed Consent since they 
will be acting as "sentinel" individuals with regard to monitoring for viral spread. Dr. David Meeker 
(Genzyme) explained that health care workers will be tested by virus culture. 
Mr. Capron asked whether the period of virus shedding is related to dosage. Dr. Meeker said that there was 
no evidence of virus shedding in Dr. Welsh’s nasal administration study using vector doses up to 1 x 10 10 IU. 
Dr. Richard Mosdcki (Genzyme) stated that the cohorts for dose escalation will be staggered between the 
bronchoscopic and aerosol administration arms of the study. If evidence of virus shedding is observed 
following lobar instillation, no patients will receive aerosol administration. 
Dr. Miller asked if fluorescein studies were conducted to determine the extent of virus spread. Dr. Dorkin 
said that similar studies have been conducted involving aerosol administration of ribavirin. Dr. Straus 
cautioned that major concerns have been raised by pulmonary physicians as a result of the ribavirin study 
because ribavirin was detected on the subject’s face and in the environment. Dr. Dorkin responded that 
HEPA filtration will provide more effective containment. HEPA filtration was not employed in the ribavirin 
study. Dr. Miller emphasized that additional studies must be conducted to determine the extent of virus 
transmission. Dr. Parkman agreed that a mock experiment involving aerosol administration of fluorescein 
labelled particles would be the preferred experimental design. Dr. Dorkin agreed to conduct the proposed 
fluorescein experiments and provide this data to the RAC. 
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Recombinant DNA Research, Volume 20 
