Evidence map›Paper›PMID 26149841›Full record

Trial reportThe Lancet. Respiratory medicine2015

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

Eric W F W Alton, David K Armstrong, Deborah Ashby, Katie J Bayfield, Diana Bilton, Emily V Bloomfield, A Christopher Boyd, June Brand, Ruaridh Buchan, Roberto Calcedo and 71 more

Erratum issued Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Respiratory medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01621867 (A Randomised, Double-blind, Placebo-controlled Phase 2B Clinical Trial of Repeated Application of Gene Therapy in Patients With Cystic Fibrosis), which is not on this map. Cited by 199 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed, 3 pooled it
39.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01621867 phase2completednot on this map

A Randomised, Double-blind, Placebo-controlled Phase 2B Clinical Trial of Repeated Application of Gene Therapy in Patients With Cystic Fibrosis

TypeinterventionalSponsorImperial College LondonRan2012 to 2014Enrolled130ConditionsCystic FibrosisArmspGM169/GL67A, Placebo
3 · Its place in the literature

Who cites it

199 citing papers in PubMed, 3 syntheses or guidelines pooled it, 420 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

139 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

81 authors at 14 institutions in 3 countries.

Eric W F W AltonImperial College London, London, UK. Electronic address: e.alton@imperial.ac.uk.
David K ArmstrongRoyal Hospital for Sick Children, Edinburgh, UK.
Deborah AshbyImperial College London, London, UK.
Katie J BayfieldImperial College London, London, UK.
Diana BiltonRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Emily V BloomfieldImperial College London, London, UK.
A Christopher BoydCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
June BrandCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ruaridh BuchanWestern General Hospital, Edinburgh, UK.
Roberto CalcedoGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Paula CarvelliImperial College London, London, UK.
Mario ChanImperial College London, London, UK.
Seng H ChengGenzyme, a Sanofi Company, Framingham, MA, USA.
D David S CollieThe Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, UK.
Steve CunninghamRoyal Hospital for Sick Children, Edinburgh, UK.
Heather E DavidsonCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Gwyneth DaviesImperial College London, London, UK.
Jane C DaviesImperial College London, London, UK.
Lee A DaviesNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Maria H DewarWestern General Hospital, Edinburgh, UK.
Ann DohertyCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Jackie DonovanRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Natalie S DwyerImperial College London, London, UK.
Hala I ElgmatiWestern General Hospital, Edinburgh, UK.
Rosanna F FeatherstoneImperial College London, London, UK.
Jemyr GavinoImperial College London, London, UK.
Sabrina Gea-SorliImperial College London, London, UK.
Duncan M GeddesRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
James S R GibsonCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Deborah R GillNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Andrew P GreeningWestern General Hospital, Edinburgh, UK.
Uta GriesenbachImperial College London, London, UK.
David M HansellRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Katharine HarmanImperial College London, London, UK.
Tracy E HigginsImperial College London, London, UK.
Samantha L HodgesImperial College London, London, UK.
Stephen C HydeNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Laura HyndmanCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
J Alastair InnesWestern General Hospital, Edinburgh, UK.
Joseph JacobRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Nancy JonesRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Brian F KeoghRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Maria P LimberisGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Paul Lloyd-EvansNHS Blood and Transplant, Bristol, UK.
Alan W MacleanCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Michelle C ManvellImperial College London, London, UK.
Dominique McCormickNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Michael McGovernWestern General Hospital, Edinburgh, UK.
Gerry McLachlanThe Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, UK.
Cuixiang MengImperial College London, London, UK.
M Angeles MonteroRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Hazel MilliganWestern General Hospital, Edinburgh, UK.
Laura J MoyceNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Gordon D MurrayUsher Institute of Population Health Sciences and Informatics and Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Andrew G NicholsonRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Tina OsadolorRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Javier Parra-LeitonCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
David J PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ian A PringleNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Emma K PunchImperial College London, London, UK.
Kamila M PytelImperial College London, London, UK.
Alexandra L QuittnerUniversity of Miami, Miami, FL, USA.
Gina RivelliniImperial College London, London, UK.
Clare J SaundersImperial College London, London, UK.
Ronald K ScheuleGenzyme, a Sanofi Company, Framingham, MA, USA.
Sarah SheardRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Nicholas J SimmondsRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Keith SmithNHS Blood and Transplant, Bristol, UK.
Stephen N SmithImperial College London, London, UK.
Najwa SoussiImperial College London, London, UK.
Samia SoussiImperial College London, London, UK.
Emma J SpearingImperial College London, London, UK.
Barbara J StevensonCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Stephanie G Sumner-JonesNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Minna TurkkilaImperial College London, London, UK.
Rosa P UretaImperial College London, London, UK.
Michael D WallerImperial College London, London, UK.
Marguerite Y WasowiczImperial College London, London, UK.
James M WilsonGene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Paul Wolstenholme-HoggGenzyme, a Sanofi Company, Framingham, MA, USA.
UK Cystic Fibrosis Gene Therapy Consortium
Imperial College London · GBUniversity of Edinburgh · GBUniversity of Oxford · GBRoslin Institute · GBNHS Blood and Transplant · GBSanofi (France) · FRUniversity of Miami · USFramingham State University · USRoyal Hospital for Sick Children · GBUniversity of Pennsylvania · USPhiladelphia University · USRoyal Brompton & Harefield NHS Foundation Trust · GBRoyal Hospital for Children · GBWestern General Hospital · GB

Funding

Medical Research Council MC_PC_12033
6 · The paper itself

Abstract

backgroundLung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis.

methodsWe did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867.

findingsBetween June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups.

interpretationMonthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials.

fundingMedical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Programme.

Indexed as

Administration, InhalationAdolescentAdultChildCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDouble-Blind MethodFemaleForced Expiratory VolumeGenetic TherapyHumansLiposomesMaleMutationNebulizers and VaporizersPlasmidsCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorLiposomes

Identifiers

PMID26149841
PMCPMC4673100
OpenAlexW1922064584

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.