Repeated application of gene therapy in cystic fibrosis patients

• Register: ISRCTN
• Last refreshed on: 19 February 2018
• Main ID: ISRCTN71164341
• Date of registration: 17/05/2012
• Prospective Registration: No
• Primary sponsor: Imperial College London (UK)
• Public title: Repeated application of gene therapy in cystic fibrosis patients
• Scientific title: Randomised, double-blind, placebo-controlled phase IIB clinical trial of repeated application of gene therapy in patients with cystic fibrosis
• Date of first enrolment: 01/03/2012
• Target sample size: 130
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN71164341
• Study type: Interventional
• Study design: Randomised double-blind placebo-controlled phase IIB (Treatment)
• Phase: Phase II

Countries of recruitment

United Kingdom

Contacts

• Name: Eric Alton

Key inclusion & exclusion 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:
4.1. Not on any additional antibiotics (excluding routine, long-term treatments) for the previous 2 weeks
4.2. No increase in symptoms such as change in sputum production/colour, increased wheeze or breathlessness over the previous 2 weeks
4.3. No change in regular respiratory treatments over the previous 4 weeks
4.4. 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 Gene Therapy Advisory Committee [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 general practitioner (GP) of participation in study
Exclusion criteria: 1. Infection with Burkholderia cepacia complex organisms, Methicillin-resistant Staphylococcus aureus (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:
8.1. Moderate/severe CF liver disease (varices or significant, sustained elevation of transaminases: ALT/ AST>100 IU/l)
8.2. Significant renal impairment (serum creatinine > 150 mol/l)
8.3. Significant coagulopathy (bronchoscopic group only)
9. Receiving second line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations
10. Pregnant or breastfeeding

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Cystic fibrosis
Nutritional, Metabolic, Endocrine
Cystic fibrosis

Intervention(s)

Administration of 5 ml pGM169/GL67A or placebo (0.9% saline) via nebuliser to the lungs every 4 weeks for 12 doses
Administration of 2 ml pGM169/GL67A or placebo (0.9% saline) via nasal spray to the nose every 4 weeks for 12 doses (subgroup only)

Primary Outcome(s)

Relative change in percent predicted FEV1 after 12 doses

Secondary Outcome(s)

1. Efficacy:
1.1. Relative change in other spirometric measures
1.2. Lung clearance index
1.3. Change in body weight
1.4. Chest CT scan
1.5. Quality of Life Questionnaires
1.6. Exercise capacity
1.7. Activity monitoring
1.8. Serum calprotectin
1.9. Sputum culture
1.10. Sputum weight, cell counts and inflammatory markers
1.11. Frequency of additional antibiotics for increased respiratory symptoms
2. Clinical examination
3. Transcutaneous oxygen saturation
4. Serum inflammatory markers (CRP, white blood cell count, IL-6)
5. Renal and hepatic function
6. Gas transfer
7. Bronchial bood flow
8. Immune response markers (anti-nuclear and double-stranded DNA antibodies, CFTR-specific T cell responses)
9. Endobronchial histology (subgroup only)
10. Gene expression outcomes (subgroups only):
10.1. Transgene mRNA expression in nasal and lower airway brushing samples
10.2. Potential difference measurements in nose and bronchi

Secondary ID(s)

2011-004761-33

CRO1881 EudraCT: 2011-004761-33

Source(s) of Monetary Support

National Institute for Health Research, Medical Research Council

Ethics review

Status:
Approval date:
Contact:

1. Gene Therapy Advisory Committee, 08/03/2012, ref: GTAC 184 2. Medicines and Healthcare products Regulatory Agency (MHRA), 02/02/2012, ref: 19174/0316/001-0001

Results

• Results available: Yes
• Date Completed: 31/03/2014