E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The medical condition is emphysema and will be investigated in subjects with alpha 1-antitrypsin deficiency. |
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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 | 10001811 |
E.1.2 | Term | Alpha-1 proteinase inhibitor deficiency |
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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 | 10014563 |
E.1.2 | Term | Emphysema pulmonary |
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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 | 10010952 |
E.1.2 | Term | COPD |
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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 | 10006458 |
E.1.2 | Term | Bronchitis chronic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Neutrophilic inflammation is central to the pathogenesis of emphysema but non-invasive, reproducible methods for measurement have not been available. 18FDG PET / CT is a new imaging method that allows quantitative spatial assessment of lung inflammation and is a potential outcome measure of anti-inflammatory therapy. Alpha 1-antitrypsin augmentation therapy is available in some EU and US states for the modification of emphysema progression in subjects with alpha 1-antitrypsin deficiency. It is proposed to assess the anti-inflammatory efficacy of augmentation therapy in subjects with inherited deficiency and in subjects with usual COPD. Comparison of global lung inflammatory burden will be made between these two groups and normal individuals and the anti-inflammatory efficacy of augmentation therapy will be assessed in subjects with emphysema . |
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E.2.2 | Secondary objectives of the trial |
The temporal and spatial relationships between inflammation and emphysema are poorly defined. It will be possible to link 18FDG PET imaging data on inflammation with CT data on emphysema severity and distribution in order to explore the realtionship between causation and morphological change. This will improve understanding of the pathogenesis of emphysema, in particular, whether inflamation occurs in areas of established emphysematous damage, or in lung regions where emphysema cannot yet be demonstrated. In addition, it will be possible to identify whether anti-inflammatory efficacy is influenced by disease stage or emphysema distribution. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Three subject groups of individuals over the age of 50 years will be studied. Healthy never smokers age 50-70 years, no evidence of lung disease, FEV1>75% predicted, FEV1/VC>70%, no relevant medical or mental disorder, able to give informed consent.
Patients with an emphysema COPD phenotype (and normal alpha 1-antitrypsin phenotype), no other active lung disease, FEV1<75% predicted, FEV1/VC<70%, KCO<80% predicted (or known emphysema on previous CT scan), fewer than two acute exacerbation in the previous 12 months and no recent exacerbations, no smoking history within the preceding 12 months, no other relevant medical or mental disorder, able to give informed consent.
Patients with an emphysema COPD phenotype (PiZ alpha 1-antitrypsin phenotype, no other active lung disease, FEV1<75% predicted, FEV1/VC<70%, KCO<80% predicted (or known emphysema on previous CT scan), fewer than two acute exacerbation in the previous 12 months and no recent exacerbations, no smoking history within the preceding 12 months, no other relevant medical or mental disorder, able to give informed consent. |
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E.4 | Principal exclusion criteria |
Age <50 or >80 Continued smoking Frequent or recent acute exacerbations of COPD Other lung disorder Relevant medical or mental illness Diabetes
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E.5 End points |
E.5.1 | Primary end point(s) |
Global neutrophilic inflammation within the lung estimated from Patlak plots of 18FDG uptake measured by PET CT imaging. Individual patients will act as their own controls by comparing imaging before and after treatment. Tretament efficacy will be assessed by between group comparison. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
pathogenic mechanism of emphysema, proof of principle study of FDG PET CT imaging. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
comparison between alpha 1-deficiency, usual COPD and normal controls |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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The completion of 12 weeks of intra-venous augmentation therapy, coincident with second PET CT scan. |
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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 | |
E.8.9.1 | In the Member State concerned days | |