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    Summary
    EudraCT Number:2011-004761-33
    Sponsor's Protocol Code Number:CRO1881
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-12-14
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2011-004761-33
    A.3Full title of the trial
    A randomised double-blind placebo-controlled Phase 2B clinical trial of repeated application of gene therapy in patients with cystic fibrosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Repeated application of gene therapy in patients with cystic fibrosis
    A.3.2Name or abbreviated title of the trial where available
    Repeated application of gene therapy in patients with CF v01-010204
    A.4.1Sponsor's protocol code numberCRO1881
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImperial College
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNHS National Institute for Health Research (NIHR)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImperial College
    B.5.2Functional name of contact pointEric Alton
    B.5.3 Address:
    B.5.3.1Street AddressDepartment of Gene Therapy, National Heart and Lung Institute, Manresa Road
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSW3 6LR
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number 44 207 351 8339
    B.5.5Fax number 44 207 351 8340
    B.5.6E-maile.alton@ic.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namepGM169/GL67A
    D.3.4Pharmaceutical form Inhalation solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntranasal use (Noncurrent)
    Inhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive namepGM169/GL67A
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number2.5 to 2.8
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboInhalation solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cystic fibrosis
    E.1.1.1Medical condition in easily understood language
    Cystic fibrosis
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10011763
    E.1.2Term Cystic fibrosis lung
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    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
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    All subjects will receive 12 doses of pGM169/GL67A nebulised to the lung at intervals of 4 weeks over a 48 week period.

    Subgroups of patients will be enrolled for gene expression measurement in both nose (at least n=20) and lower airway via bronchoscopy (at least n=20). A subject could be included in both of these subgroups if suitable and willing.

    The majority of subjects have been participating in a longitudinal "Run-in" study and have extensive pre-dosing data; these patients will undergo a single screening visit prior to dosing. Subjects who are new to the programme will undergo an initial Introductory visit at which suitability will be assessed prior to the formal screening visit.

    The sub-groups are fully described in the current version of the over-arching clinical protocol (attached).
    E.3Principal 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.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary end point(s)
    Relative change in percent predicted FEV1 from baseline after the 12th dose.
    E.5.1.1Timepoint(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.
    E.5.2Secondary 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).
    E.5.2.1Timepoint(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.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last visit of the last study subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 55
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 55
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 75
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    children with CF aged 12 years and above. Consent will be sought from parent/ guardian and assent from the child
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state130
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 130
    F.4.2.2In the whole clinical trial 130
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subject will continue with standard cystic fibrosis clinical care.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Medicines for Children Research Network
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-02-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-03-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-05-30
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