Cystic FibrosisPhase 1/2NCT00789867
Single Dose of pGM169/GL67A in CF Patients
A Phase 1/2 study testing pGM169/GL67A in people with Cystic Fibrosis, run by Imperial College London at 1 site in United Kingdom.
Trial 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 more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- pGM169/GL67A
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2008to Dec 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- Significant comorbidity including:
- Moderate/severe CF liver disease
- Significant renal impairment
- Significant coagulopathy
- Receiving 2nd line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations
- Pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Safety and Gene Expression With a Single Dose of pGM169/GL67A Administered to the Nose and Lung of Individuals With Cystic Fibrosis
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.
- Conditions
- Cystic Fibrosis
- Being tested
- pGM169/GL67A
- Keywords
- Single dose, Pilot, Safety, Gene expression, Tolerability, CFTR gene, Cystic fibrosis, Non-viral
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pGM169/GL67ADrug
Also called 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67A
Received a nebulized dose via an breath-actuated nebulizer
| Study group | Role | What they receive |
|---|---|---|
| 20ml pGM169/GL67A | Experimental | Received a nebulized dose 20ml via an breath-actuated nebulizer Receives: Drug: pGM169/GL67A |
| 10ml pGM169/GL67A | Experimental | Received a nebulized dose 10ml via an breath-actuated nebulizer Receives: Drug: pGM169/GL67A |
| 5ml pGM169/GL67A | Experimental | Received a nebulized dose 5ml via an breath-actuated nebulizer Receives: Drug: pGM169/GL67A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body Maximum Temperature
Measured: 6-8h
Blood Leukocytes
Blood leukocytes measure
Measured: 8h
Blood Neutrophils
Blood neutrophils measures
Measured: 8h
FEV1 Relative % Drop
FEV1 relative % drop measure
Measured: 8h
FVC Relative % Drop
FVC relative % drop measure
Measured: 6h
Lung Clearance Index - LCI
Lung clearance index measure is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout technique.
Measured: 8h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionAug 2009
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust, University of Oxford, University of Edinburgh, Cystic Fibrosis Trust, University of Pennsylvania
- Responsible party
- Sponsor
- Investigators
- Eric Alton, Study director, Imperial College LondonJane C Davies, Principal investigator, Imperial College LondonUta Griesenbach, Principal investigator, Imperial College LondonSteve Hyde, Principal investigator, University of OxfordDeborah Gill, Principal investigator, University of OxfordDavid Porteous, Principal investigator, Edinburgh UniversityChris Boyd, Principal investigator, Edinburgh UniversityAlastair Innes, Principal investigator, Edinburgh University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00789867
- Sponsor's protocol ID
- cro851
- Status last verified
- Jan 2020
- First submitted
- 11 Nov 2008
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 10459902Alton 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
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Safety and Gene Expression With a Single Dose of pGM169/GL67A Administered to the Nose and Lung of Individuals With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00789867
- Acronym / sponsor ID
- cro851
- Conditions
- Cystic Fibrosis
- Keywords
- Single dose, Pilot, Safety, Gene expression, Tolerability, CFTR gene, Cystic fibrosis, Non-viral
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust, University of Oxford, University of Edinburgh, Cystic Fibrosis Trust, University of Pennsylvania
- Study start
- Nov 2008 (actual)
- Primary completion
- Aug 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 13 Nov 2008 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 20ml pGM169/GL67A | Experimental | Drug: pGM169/GL67AReceived a nebulized dose 20ml via an breath-actuated nebulizer |
| 10ml pGM169/GL67A | Experimental | Drug: pGM169/GL67AReceived a nebulized dose 10ml via an breath-actuated nebulizer |
| 5ml pGM169/GL67A | Experimental | Drug: pGM169/GL67AReceived a nebulized dose 5ml via an breath-actuated nebulizer |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pGM169/GL67AAlso: 5ml pGM169/GL67A, 10ml pGM169/GL67A and 20ml pGM169/GL67AReceived a nebulized dose via an breath-actuated nebulizer | Drug | 10ml pGM169/GL67A, 20ml pGM169/GL67A, 5ml pGM169/GL67A |
Primary outcome
Body Maximum Temperature
Time frame: 6-8h
Blood Leukocytes
Time frame: 8h
Blood leukocytes measure
Blood Neutrophils
Time frame: 8h
Blood neutrophils measures
FEV1 Relative % Drop
Time frame: 8h
FEV1 relative % drop measure
FVC Relative % Drop
Time frame: 6h
FVC relative % drop measure
Lung Clearance Index - LCI
Time frame: 8h
Lung clearance index measure is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout technique.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10459902Alton 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.
- Results publication: PubMed 26623687Alton 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.
- UK CF Gene Therapy Consortium websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Alton study director
Imperial College London
Jane C Davies principal investigator
Imperial College London
Uta Griesenbach principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing pGM169/GL67A in people with Cystic Fibrosis, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Body Maximum Temperature (time frame: 6-8h). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00789867, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.