Repeated Application of Gene Therapy in CF Patients

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Cystic fibrosis is a genetic condition where epithelial cells, including from the respiratory tract, have an abnormal function of a surface protein, the cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from abnormal gene expression. The trial will assess the clinical efficacy, safety & tolerability and gene expression following repeated nebulised doses of a gene product coding for a normal CFTR protein, with the primary outcome of the trial assessing lung function.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Imperial College London
• Collaborators: Royal Brompton & Harefield NHS Foundation Trust; University of Edinburgh; University of Oxford

Criteria

Inclusion Criteria:

1. Cystic fibrosis confirmed by sweat testing or genetic analysis

2. Males and females aged 12 years and above

3. Forced expiratory volume in the 1st second (FEV1) between 50 & 90% predicted inclusive (Stanojevic reference equations).

4. Clinical stability at screening defined by:

1. Not on any additional antibiotics (excluding routine, long-term treatments) for the previous 2 weeks

2. No increase in symptoms such as change in sputum production/colour, increased wheeze or breathlessness over the previous 2 weeks

3. No change in regular respiratory treatments over the previous 4 weeks

4. If any of these apply, entry into the study can be deferred

5. Prepared to take effective contraceptive precautions for the duration of their participation in the study and for 3 months thereafter (as stated in GTAC guidelines)

6. If taking regular rhDNase (pulmozyme) is willing, and considered able by independent medical carers, to withhold treatment for 24 hours before and 24 hours after the gene therapy dose (nebulised doses only)

7. Written informed consent obtained

8. Permission to inform their general practitioner of participation in study

Exclusion Criteria:

1. Infection with Burkholderia cepacia complex organisms, MRSA or M. abscessus

2. Significant nasal pathology including polyps, clinically-significant rhinosinusitis, or recurrent severe epistaxis (nose bleeds) (nasal cohort only)

3. Chloride secretory response on nasal PD of > 5 mV (nasal cohort only; will only be known after first measurement)

4. Acute upper respiratory tract infection within the last 2 weeks (entry can be deferred)

5. Previous spontaneous pneumothorax without pleurodesis (bronchoscopic subgroup only)

6. Recurrent severe haemoptysis (bronchoscopic subgroup only)

7. Current smoker

8. Significant comorbidity including:

1. Moderate/severe CF liver disease (varices or significant, sustained elevation of transaminases: ALT/ AST>100 IU/l)

2. Significant renal impairment (serum creatinine > 150 mmol/l)

3. Significant coagulopathy (bronchoscopic group only)

9. Receiving 2nd line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations

10. Pregnant or breastfeeding