E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and gene transfer resulting from a single dose of pGM169/GL67A to the lungs and nose of patients with cystic fibrosis |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Cystic fibrosis confirmed by sweat testing or genetic analysis 2. Males and females aged 16 years and above 3. Forced expiratory volume in the 1st second (FEV1) > 60% predicted values [ we consider that this population of patients will have relatively clear airways and thus the best chance of successful gene transfer] 4. Clinical stability at entry defined by: a. Not on any extra antibiotics (excluding routine, long-term treatments) for the previous 2 weeks b. No increase in symptoms such as change in sputum production/colour, increased wheeze or breathlessness over the previous 2 weeks c. No change in regular respiratory treatments over the previous 4 weeks d. If any of these apply, entry into the study can be deferred 5. Prepared to take effective contraceptive precautions for the duration of their participation in the study and for 3 months thereafter [as stated in GTAC guidelines] 6. If taking regular rhDNase (pulmozyme) is willing, and considered able by independent medical carers, to withhold treatment for 48 hours around the time of the gene therapy dose 7. Written informed consent obtained 8. Permission to inform GP of participation in study
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E.4 | Principal exclusion criteria |
1. Infection with Burkholderia cepacia complex organisms or MRSA [for infection control reasons]) 2. Significant nasal pathology including polyps, clinically-significant rhinosinusisitis, or recurrent severe epistaxis (nose bleeds) [either dose delivery or assays may be adversely affected] 3. Acute upper respiratory tract infection within the last 2 weeks (entry can be deferred) 4. Previous spontaneous pneumothorax, unless patient has had a subsequent pleurodesis [this subgroup are at increased risk of future pneumothoraces] 5. Recurrent severe haemoptysis [this group may be at increased risk of bleeding due to bronchoscopy and biopsy] 6. Current smoker (will be assessed by measuring cotinine level prior to study entry) [we cannot determine the effect of smoking on gene transfer or assays] 7. Significant comorbidity including: a. Moderate/severe CF liver disease (varices or significant, sustained elevation of transaminases: ALT/ AST>100 IU/l) b. Significant renal impairment (serum creatinine > 150 micro mol/l) c. Significant coagulopathy 8. Receiving 2nd line immunosuppressant drugs such as methotrexate, cyclosporine, intravenous immunoglobulin preparations 9. Pregnant or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: clinical examination, oxygen saturation, spirometry, routine clinical blood samples, chest CT, gas transfer (TLCO) Expression: transgene mRNA and CFTR protein expression in airway samples; potential difference measurements in nose and bronchi
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial 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
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Last visit of the last study subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |