Phase I Study of Liposome-Mediated Gene Transfer in Patients With Cystic Fibrosis
Phase I Study of Liposome-Mediated Gene Transfer in Patients With Cystic Fibrosis
OBJECTIVES:

 Evaluate the efficacy and safety of lipid-mediated transfer of the cystic fibrosis
 transmembrane conductance regulator gene to nasal epithelium in patients with cystic
 fibrosis.
PROTOCOL OUTLINE: Cystic fibrosis transmembrane conductance regulator (CFTR) gene complexed
 with lipid is administered intranasally to the right inferior turbinate. Lipid without CFTR
 is administered to the left nostril as a control.

 Cohorts of 3 patients are given successively lower doses of CFTR, each dose complexed with
 500 micrograms of lipid.

 Patients are followed at days 2-12, 15, and 21, then every 3-4 days for 3 weeks, every 2-3
 weeks for 10 weeks, and every 3 months thereafter.
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics-- Cystic fibrosis (CF), i.e.: Sweat chloride greater than 60
 mEq/L Clinical manifestations of CF Homozygous delta F508 mutation preferred Compound
 heterozygotes for F508 mutation with pancreatic insufficiency eligible FEV1 greater than
 40% of predicted PO2 at least 60 mm Hg on room air No acute or recurrent sinusitis No
 obstructive nasal polyposis No pneumothorax or hemoptysis, e.g., more than 250 mL blood
 within 24-hour period, within past year No unstable lung disease with worsening pulmonary
 symptoms, arterial blood gas, or pulmonary function tests within 2 weeks prior to entry No
 pulmonary exacerbation within 4 weeks prior to entry --Prior/Concurrent Therapy-- At least
 2 months since participation in any other clinical study At least 2 months since DNase At
 least 4 months since corticosteroids --Patient Characteristics-- Cardiac: No severe cardiac
 disease Other: No other severe organ system disease, e.g., juvenile-type diabetes mellitus
 No pregnant women