The European Society of Gene and Cell Therapy Conference, Helsinki, 2015
The UK Cystic Fibrosis Gene Therapy Consortium has undertaken an extensive pre-clinical programme, including repeat-dose toxicology studies in mice and sheep, together with a Phase 1/2a safety study in Cystic Fibrosis (CF) patients to assess aerosol delivery of non-viral plasmid DNA/liposomes to the lungs.
The formulation is composed of GL67A liposomes complexed with plasmid pGM169, which is completely free of CpG dinucleotides and directs persistent high-level expression of codon-optimised CFTR under the control of the hCEFI promoter/enhancer (Hyde et al 2008 Nature Biotechnology 26: 549-551).
The Phase 1/2a trial in CF patients identified a safe (5ml) aerosol dose delivered to the lungs via a Trudell AeroEclipse II nebuliser. In a follow-on Phase 2b study, CF patients with an FEV1 % predicted lung function of between 50 and 90% were recruited to measure potential clinical benefit following delivery of 12 aerosol doses at monthly (28 ± 5 day) intervals.
The double-blind, placebo-controlled trial compared the above formulation with 0.9% saline in a 1:1 randomisation. The Per Protocol patient group (pre-defined as receiving 9 or more doses) consisted of 116 patients (52 Placebo and 64 Active). Two small (n=24) patient sub-groups also underwent either additional nasal administration, or bronchoscopic measurements, to evaluate molecular surrogates (2:1 randomisation Active: Placebo).
Data for safety and primary/secondary efficacy outcome measures will be presented.
Supported by the NIHR EME programme and the CF Trust.