Table 2.

U.K. Cystic Fibrosis Gene Therapy Program

Phase	Objectives	Progression criteria
Preclinical selection and development of a GTA suitable for repeated administration to patients with CF	Selection of pGM169/GL67A	1. Transfection of AECs 2. Low toxicity 3. Repeat administration feasible 4. Stability in nebulizer 5. GMP production feasible
Tracking study	Validation of putative end-point assays in patients undergoing exacerbations	Selection of end points that respond to conventional treatment
Single-dose phase I/IIa pilot trial	1. Selection of suitable dose for MDT 2. Confirmation of dosing interval in patients with CF	1. Suitable dose: 5 ml of pGM169/GL67A per dose 2. Dosing interval: Monthly for 12 months
Run-in study	1. Selection of primary and secondary end points 2. Characterization of most suitable patient population for MDT trial	1. Primary end point: Percent change in relative FEV1 from baseline 2. Inclusion of patients >12 years and with baseline FEV1 of 50 to 90%
Multidose murine and ovine regulatory-compliant toxicology studies	Prove safety in animal models	1. No chronic inflammation 2. No remodeling of lung 3. No extrapulmonary effects
Multidose, double-blinded, placebo-controlled phase IIb trial	Significant difference in primary end point comparing active and placebo groups	Depending on outcome of trial

AECs, airway epithelial cells; CF, cystic fibrosis; FEV₁, forced expiratory volume in the first second; GMP, Good Manufacturing Process; GTA, gene transfer agent; MDT, multidose trial.