Repeated application of gene therapy in patients with cystic fibrosis

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2011-004761-33-GB
• Date of registration: 14/12/2011
• Prospective Registration: Yes
• Primary sponsor: Imperial College
• Public title: Repeated application of gene therapy in patients with cystic fibrosis
• Scientific title: A randomised double-blind placebo-controlled Phase 2B clinical trial of repeated application of gene therapy in patients with cystic fibrosis - Repeated application of gene therapy in patients with CF v01-010204
• Date of first enrolment: 08/03/2012
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004761-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Eric Alton
• Affiliation: Imperial College

• Name: Eric Alton
• Affiliation: Imperial College

Key inclusion & exclusion criteria

Inclusion criteria:
1. Confirmed diagnosis of Cystic Fibrosis.
2. =12 years.
3. Mild to moderate cystic fibrosis lung disease based on forced expiratory volume in the first second (FEV1) of 50-90% predicted
4. Any CFTR mutation.
5. Clinical stability over the 4 weeks prior to the first dose.
6. Written informed consent from the patient (aged 16 years and above) or parent if a child aged 12-15 years.
7. Assent from a child aged 12-15 years.
8. Willing to adhere to contraceptive requirements.
Are the trial subjects under 18? yes
Number of subjects for this age range: 55
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Current participation in another interventional trial.
2. Infection with Burkholderia cepacia complex organisms, Mycobacterium abscessus or MRSA (unless local infection control guidelines can be adhered to).
3. Previous spontaneous pneumothorax unless pleurodesed (bronchoscopic group only).
4. Recurrent severe haemoptysis.
5. Current smoker.
6. Significant comorbidity eg severe CF liver disease or renal impairment.
7. Using second line immunosuppressants.
8. Pregnant or breast-feeding.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic fibrosis
MedDRA version: 20.0 Level: PT Classification code 10011763 Term: Cystic fibrosis lung System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: pGM169/GL67A
Pharmaceutical Form: Inhalation solution
Other descriptive name: pGM169/GL67A
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 2.5-2.8
Pharmaceutical form of the placebo: Inhalation solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The baseline will be defined as the mean of Screening and Pre-dose 1 values, whilst the end value will be the mean of measures obtained 14 and 28 days after the 12th dose.

Main Objective: The clinical study has three main objectives:

1. To assess the clinical benefit of pGM169/GL67A when administered on a monthly basis over a period of a year.
2. To assess the safety and tolerability of pGM169/GL67A over the same period.
3. To assess gene expression directed by pGM169/GL67A over the same period.

Secondary Objective: The clinical study has six secondary objectives:

1. Will tests that measure correction of the basic CF defect correlate with changes in patient lung function and clinical symptoms.
2. Will tests that measure correction of the basic CF defect in the nose correlate with those measured in the lung.
3. Will tests that measure correction of the basic CF defect improve with repeated administration of gene therapy.
4. If some subjects respond well to treatment with gene therapy, as judged by either the primary (FEV1 lung function) or secondary (quality of life questionnaire, chest CT, lung clearance index etc) outcomes, and some do not, will it be possible to find a common reason.
5. Will any of the secondary outcome tests (quality of life questionnaire, chest CT, lung clearance index etc) provide different or better information than the primary outcome test (the FEV1 lung function test), allowing them to be used in future trials.
6. Will the laboratory and toxicology data we collect

Primary end point(s): Relative change in percent predicted FEV1 from baseline after the 12th dose.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The secondary end points will be assessed at the close of the study, once all patients have received 12 doses of pGM169/GL67A or placebo.

Secondary end point(s): Efficacy: Lung clearance index, chest CT scan, Quality of Life measures (using the CFQ-UK validated questionnaire), other spirometric markers, exercise capacity, activity monitoring, serum calprotectin, sputum microbiology, cell counts and soluble inflammatory markers (IL-8 and neutrophil elastase).

Safety: The above efficacy measures plus clinical examination, oxygen saturation, frequency of additional antibiotics for respiratory exacerbations, sputum culture, serum inflammatory markers (white cell count, C-Reactive Protein and IL-6), renal and hepatic function, and gas transfer. Inflammation will be assessed by visual inspection and endobronchial biopsy in the bronchoscopic subgroup.

Gene expression: Transgene mRNA and potential difference measurements in the nose and lung (subgroups only).

Secondary ID(s)

CRO1881

Source(s) of Monetary Support

NHS National Institute for Health Research (NIHR)

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 08/06/2019
• Date Completed: 30/05/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-004761-33/results