Repeated Application of Gene Therapy in CF Patients
A Randomised, Double-blind, Placebo-controlled Phase 2B Clinical Trial of Repeated Application of Gene Therapy in Patients With Cystic Fibrosis
2 other identifiers
interventional
130
1 country
3
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2012
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
June 14, 2012
CompletedFirst Posted
Study publicly available on registry
June 18, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2014
CompletedOctober 22, 2015
November 1, 2012
2 years
June 14, 2012
October 21, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Relative change in percent predicted FEV1 after 12 doses of gene product
12-months
Secondary Outcomes (3)
EFFICACY
12-months
SAFETY
12-months
GENE EXPRESSION(subgroups only)
12-months
Study Arms (2)
pGM169/GL67A (CFTR Gene/Lipid Vector)
ACTIVE COMPARATORPlacebo
PLACEBO COMPARATORInterventions
5ml Gene Product/Lipid Vector pGM169/GL67A nebulised; 2ml nasal application of pGM169/GL67A in addition to 5ml nebulised gene product (Nasal Subgroup)
5ml Nebulised non-active placebo; 2ml nasal administration of non-active placebo (nasal subgroup)
Eligibility Criteria
You may qualify if:
- Cystic fibrosis confirmed by sweat testing or genetic analysis
- Males and females aged 12 years and above
- Forced expiratory volume in the 1st second (FEV1) between 50 \& 90% predicted inclusive (Stanojevic reference equations).
- Clinical stability at screening defined by:
- Not on any additional antibiotics (excluding routine, long-term treatments) for the previous 2 weeks
- No increase in symptoms such as change in sputum production/colour, increased wheeze or breathlessness over the previous 2 weeks
- No change in regular respiratory treatments over the previous 4 weeks
- If any of these apply, entry into the study can be deferred
- 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)
- 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)
- Written informed consent obtained
- Permission to inform their general practitioner of participation in study
You may not qualify if:
- Infection with Burkholderia cepacia complex organisms, MRSA or M. abscessus
- Significant nasal pathology including polyps, clinically-significant rhinosinusitis, or recurrent severe epistaxis (nose bleeds) (nasal cohort only)
- Chloride secretory response on nasal PD of \> 5 mV (nasal cohort only; will only be known after first measurement)
- Acute upper respiratory tract infection within the last 2 weeks (entry can be deferred)
- Previous spontaneous pneumothorax without pleurodesis (bronchoscopic subgroup only)
- Recurrent severe haemoptysis (bronchoscopic subgroup only)
- Current smoker
- Significant comorbidity including:
- Moderate/severe CF liver disease (varices or significant, sustained elevation of transaminases: ALT/ AST\>100 IU/l)
- Significant renal impairment (serum creatinine \> 150 mmol/l)
- Significant coagulopathy (bronchoscopic group only)
- Receiving 2nd line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations
- Pregnant or breastfeeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Imperial College Londonlead
- University of Edinburghcollaborator
- University of Oxfordcollaborator
- Royal Brompton & Harefield NHS Foundation Trustcollaborator
Study Sites (3)
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Royal Hospital for Sick Children
Edinburgh, EH9 1LF, United Kingdom
Royal Brompton Hospital
London, SW3 6NP, United Kingdom
Related Publications (3)
Alton EW, Stern M, Farley R, Jaffe A, Chadwick SL, Phillips J, Davies J, Smith SN, Browning J, Davies MG, Hodson ME, Durham SR, Li D, Jeffery PK, Scallan M, Balfour R, Eastman SJ, Cheng SH, Smith AE, Meeker D, Geddes DM. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet. 1999 Mar 20;353(9157):947-54. doi: 10.1016/s0140-6736(98)06532-5.
PMID: 10459902RESULTMiah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.
PMID: 31215818DERIVEDAlton EWFW, Armstrong DK, Ashby D, Bayfield KJ, Bilton D, Bloomfield EV, Boyd AC, Brand J, Buchan R, Calcedo R, Carvelli P, Chan M, Cheng SH, Collie DDS, Cunningham S, Davidson HE, Davies G, Davies JC, Davies LA, Dewar MH, Doherty A, Donovan J, Dwyer NS, Elgmati HI, Featherstone RF, Gavino J, Gea-Sorli S, Geddes DM, Gibson JSR, Gill DR, Greening AP, Griesenbach U, Hansell DM, Harman K, Higgins TE, Hodges SL, Hyde SC, Hyndman L, Innes JA, Jacob J, Jones N, Keogh BF, Limberis MP, Lloyd-Evans P, Maclean AW, Manvell MC, McCormick D, McGovern M, McLachlan G, Meng C, Montero MA, Milligan H, Moyce LJ, Murray GD, Nicholson AG, Osadolor T, Parra-Leiton J, Porteous DJ, Pringle IA, Punch EK, Pytel KM, Quittner AL, Rivellini G, Saunders CJ, Scheule RK, Sheard S, Simmonds NJ, Smith K, Smith SN, Soussi N, Soussi S, Spearing EJ, Stevenson BJ, Sumner-Jones SG, Turkkila M, Ureta RP, Waller MD, Wasowicz MY, Wilson JM, Wolstenholme-Hogg P; UK Cystic Fibrosis Gene Therapy Consortium. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015 Sep;3(9):684-691. doi: 10.1016/S2213-2600(15)00245-3. Epub 2015 Jul 3.
PMID: 26149841DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Eric Alton, MD, FMedSci
Imperial College London
- PRINCIPAL INVESTIGATOR
Jane Davies, MD
Imperial College London
- PRINCIPAL INVESTIGATOR
Uta Griesenbach, PhD
Imperial College London
- PRINCIPAL INVESTIGATOR
Steve Hyde, MA, DPhil
University of Oxford
- PRINCIPAL INVESTIGATOR
Deborah Gill, PhD
University of Oxford
- PRINCIPAL INVESTIGATOR
Chris Boyd, PhD
Edinburgh University
- PRINCIPAL INVESTIGATOR
David Porteous, FMedSci
Edinburgh University
- PRINCIPAL INVESTIGATOR
Alastair Innes, PhD
Edinburgh University
- PRINCIPAL INVESTIGATOR
Steve Cunningham, PhD
Edinburgh University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 14, 2012
First Posted
June 18, 2012
Study Start
May 1, 2012
Primary Completion
May 1, 2014
Study Completion
May 1, 2014
Last Updated
October 22, 2015
Record last verified: 2012-11