Single Dose of pGM169/GL67A in CF Patients
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The study objectives are to assess safety, tolerability and gene expression after a single
      dose of non-viral CFTR gene therapy (pGM169/GL67A) administered to the nose and lungs of
      patients with cystic fibrosis.
    

Detailed description: 
      The trial is designed as single administration to nose and lung. Initially, in Part A, 3
      patients will be dosed individually one week apart with 10 ml (26.5mg pDNA) via nebuliser and
      a nasal dose equivalent to 10% of this (based on relative surface area calculations:
      conducting airways approximate 540 cm2; nasal epithelium from both nostrils approximately 40
      cm2). Based on our previous study, we do not expect any side effects of the nasal dose, but
      we are taking this opportunity, as this group will not be undergoing bronchoscopic efficacy
      measures, to assess gene transfer to the nasal epithelium. A further group of 3 patients will
      then be treated in exactly the same way with 20 ml nebulised and a 2 ml nasal dose.

      Subsequently, patients will receive doses of 2 ml (nasal) and 20 ml (nebulised). These
      patients will undergo more intensive monitoring for gene expression both before and after
      administration.

      In Part B of the protocol, we will test combinations of delivery conditions and dose in an
      attempt to identify the maximal tolerated dose. We may also use Ibuprofen or Prednisolone in
      standard clinical doses around the dosing period to reduce the inflammatory response.
      Delivery conditions include: standard nebulisation (each 5 ml over 25 minutes as in Part A),
      slow (each 5 ml over 75-150 minutes) and divided (standard rate delivery with a period of up
      to 6 hours between aliquots). With these conditions we will test the following doses until a
      tolerable dose is reached: 20 ml (no standard delivery as sufficient data already available
      from Part A); 10 ml; 5 ml; 2.5 ml. Each dosing strategy will initially be performed in a
      cohort of 3 patients although numbers may need to be increased to 6 if data are inconclusive.
      Once a satisfactory Single dose of pGM169/GL67A in CF patients; cro851 Version 10; 16.08.2010
      10 dose and nebulisation strategy has been identified, the numbers receiving this will be
      increased to 6. The maximum number of patients recruited to this arm of the study will be 30.
      Part B will also allow either these subjects or others to receive a 2 ml nasal dose with both
      pre and post-measurements of nasal PD.
    

Intervention name(s): pGM169/GL67A
Intervention type(s): Drug
Intervention description(s): Received a nebulized dose via an breath-actuated nebulizer
Other intervention name(s): 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Single dose; Pilot; Safety; Gene expression; Tolerability; CFTR gene; Cystic fibrosis; Non-viral