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CompletedNCT00789867Updated Jan 18, 2020Results posted

Single Dose of pGM169/GL67A in CF Patients

A Phase 1/2 interventional study of pGM169/GL67A in Cystic Fibrosis, sponsored by Imperial College London. Completed at 1 site in United Kingdom. Open to participants aged 16 Years to 70 Years. Per ClinicalTrials.gov, last updated 2020-01-18.

Sponsored by Imperial College London · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
35
Allocation
Randomized
Ages
16 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cystic Fibrosis

Keywords

  • Single dose
  • Pilot
  • Safety
  • Gene expression
  • Tolerability
  • CFTR gene
  • Cystic fibrosis
  • Non-viral
03

In context

Cystic Fibrosis

1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.

This study's enrollment of 35 is close to the median of 36 across 1,034 interventional studies indexed under Cystic Fibrosis.

Browse Cystic Fibrosis studies →

Lead sponsor

Imperial College London is the lead sponsor of 824 studies on the registry; 178 are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
16 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Cystic fibrosis confirmed by sweat testing or genetic analysis
  • Males and females aged 16 years and above
  • Forced expiratory volume in the 1st second (FEV1) > 60% predicted values
  • Clinical stability at entry
  • Prepared to take effective contraceptive precautions for the duration of their participation in the study and for 3 months thereafter
  • 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
  • Written informed consent obtained
  • Permission to inform GP of participation in study

Exclusion criteria

Exclusion Criteria:

  • Infection with Burkholderia cepacia complex organisms or MRSA
  • Significant nasal pathology including polyps, clinically-significant rhinosinusitis, or recurrent severe epistaxis (nose bleeds)
  • Acute upper respiratory tract infection within the last 2 weeks
  • Previous spontaneous pneumothorax without pleurodesis
  • Recurrent severe haemoptysis
  • Current smoker

  • Significant comorbidity including:

    1. Moderate/severe CF liver disease
    2. Significant renal impairment
    3. Significant coagulopathy
  • Receiving 2nd line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations
  • Pregnant or breastfeeding
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
35 participants (actual)

Study arms

  • Experimental
    20ml pGM169/GL67A

    Received a nebulized dose 20ml via an breath-actuated nebulizer

    Drug: pGM169/GL67A

  • Experimental
    10ml pGM169/GL67A

    Received a nebulized dose 10ml via an breath-actuated nebulizer

    Drug: pGM169/GL67A

  • Experimental
    5ml pGM169/GL67A

    Received a nebulized dose 5ml via an breath-actuated nebulizer

    Drug: pGM169/GL67A

Interventions

  • DrugpGM169/GL67A

    Received a nebulized dose via an breath-actuated nebulizer

    Also known as: 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A

06

What researchers measure

Primary outcomes

  1. Body Maximum Temperature

    Time frame: 6-8h

  2. Blood Leukocytes

    Blood leukocytes measure

    Time frame: 8h

  3. Blood Neutrophils

    Blood neutrophils measures

    Time frame: 8h

  4. FEV1 Relative % Drop

    FEV1 relative % drop measure

    Time frame: 8h

  5. FVC Relative % Drop

    FVC relative % drop measure

    Time frame: 6h

  6. Lung Clearance Index - LCI

    Lung clearance index measure is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout technique.

    Time frame: 8h

07

Results

Posted Jan 18, 2020

Participant flow

Participant flow — Overall Study
Milestone20 ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Started17108
Completed17108
Not completed000

Outcome measures

PrimaryBody Maximum Temperature
Time frame:
6-8h
Reported as:
Mean · celsius
Body Maximum Temperature
celsius20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Body Maximum Temperature38.6 ± 0.538.0 ± 0.737.4 ± 0.3
Statistical analysis
  • 20ml pGM169/GL67A vs 10ml pGM169/GL67A vs 5ml pGM169/GL67A · Kruskal-Wallis · p = 0.0002
PrimaryBlood Leukocytes

Blood leukocytes measure

Time frame:
8h
Reported as:
Mean · x1000000000 cells/L
Blood Leukocytes
x1000000000 cells/L20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Blood Leukocytes15.8 ± 3.214.1 ± 4.512.8 ± 3.8
Statistical analysis
  • 20ml pGM169/GL67A vs 10ml pGM169/GL67A vs 5ml pGM169/GL67A · Kruskal-Wallis · p = 0.22
PrimaryBlood Neutrophils

Blood neutrophils measures

Time frame:
8h
Reported as:
Mean · 1000000000/L
Blood Neutrophils
1000000000/L20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Blood Neutrophils13.9 ± 3.411.3 ± 4.19.8 ± 3.5
Statistical analysis
  • 20ml pGM169/GL67A vs 10ml pGM169/GL67A vs 5ml pGM169/GL67A · Kruskal-Wallis · p = 0.06
PrimaryFEV1 Relative % Drop

FEV1 relative % drop measure

Time frame:
8h
Reported as:
Mean · % of drop
FEV1 Relative % Drop
% of drop20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
FEV1 Relative % Drop24.6 ± 9.317.5 ± 7.816.8 ± 4.0
Statistical analysis
  • 20ml pGM169/GL67A vs 10ml pGM169/GL67A vs 5ml pGM169/GL67A · Kruskal-Wallis · p = 0.08
PrimaryFVC Relative % Drop

FVC relative % drop measure

Time frame:
6h
Reported as:
Mean · % drop
FVC Relative % Drop
% drop20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
FVC Relative % Drop20.7 ± 2.913.7 ± 2.214.7 ± 2.2
Statistical analysis
  • 20ml pGM169/GL67A vs 10ml pGM169/GL67A vs 5ml pGM169/GL67A · Kruskal-Wallis · p = 0.22
PrimaryLung Clearance Index - LCI

Lung clearance index measure is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout technique.

Time frame:
8h
Reported as:
Mean · index
Lung Clearance Index - LCI
index20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Lung Clearance Index - LCI0.75 ± 0.30.32 ± 0.10.32 ± .01
Statistical analysis
  • 20ml pGM169/GL67A vs 10ml pGM169/GL67A vs 5ml pGM169/GL67A · Kruskal-Wallis · p = 0.003

Adverse events

Collected over 28 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
20ml pGM169/GL67A0/17 (0%)1/17 (5.9%)14/17 (82.4%)
10ml pGM169/GL67A0/10 (0%)1/10 (10%)7/10 (70%)
5ml pGM169/GL67A0/8 (0%)0/8 (0%)1/8 (12.5%)
Most frequent serious events
Most frequent serious events
Event20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Acute pancreatitisEndocrine disorders0/171/100/8
Injury in luvula sustained from pressure of tube during bronchoscopy 03/04/2009Respiratory, thoracic and mediastinal disorders1/170/100/8
Most frequent other events
Most frequent other events
Event20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67A
Mild self limiting influenza like systemic responseImmune system disorders14/177/101/8

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67ATotal
<=18 years1102
Between 18 and 65 years169833
>=65 years0000
Age, Continuous
Age, Continuous(years)20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67ATotal
Median26.7 (17.3 to 50.1)33.2 (16.4 to 61.6)32.6 (24.3 to 46.4)27.4 (16.4 to 61.6)
Sex: Female, Male
Sex: Female, Male(Participants)20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67ATotal
Female54312
Male126523
Region of Enrollment
Region of Enrollment(participants)20ml pGM169/GL67A10ml pGM169/GL67A5ml pGM169/GL67ATotal
United Kingdom1710835
08

Study locations

1 site
  • Royal Brompton Hospital
    London, SW3 6NP, United Kingdom
09

References and documents

Publications

  • 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. PubMed 10459902 ↗
  • Alton EW, Boyd AC, Porteous DJ, Davies G, Davies JC, Griesenbach U, Higgins TE, Gill DR, Hyde SC, Innes JA; UK Cystic Fibrosis Gene Therapy Consortium *. A Phase I/IIa Safety and Efficacy Study of Nebulized Liposome-mediated Gene Therapy for Cystic Fibrosis Supports a Multidose Trial. Am J Respir Crit Care Med. 2015 Dec 1;192(11):1389-92. doi: 10.1164/rccm.201506-1193LE. No abstract available. PubMed 26623687 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 18, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00789867
Lead sponsor
Imperial College London
Collaborators
Royal Brompton & Harefield NHS Foundation Trust, University of Oxford, University of Edinburgh, Cystic Fibrosis Trust, University of Pennsylvania
Responsible party
Sponsor
First posted
Nov 13, 2008
Start date
Nov 2008
Primary completion
Aug 2009
Completion
Dec 2010
Results posted
Jan 18, 2020
Last update
Jan 18, 2020

Study contacts

Eric Alton
study director · Imperial College London
Jane C Davies
principal investigator · Imperial College London
Uta Griesenbach
principal investigator · Imperial College London
Steve Hyde
principal investigator · University of Oxford
Deborah Gill
principal investigator · University of Oxford
David Porteous
principal investigator · Edinburgh University
Chris Boyd
principal investigator · Edinburgh University
Alastair Innes
principal investigator · Edinburgh University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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