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| Name | Class |
|---|---|
| University of Sheffield | OTHER |
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The investigators aim to recruit 32 people with COPD who have frequent exacerbations and high eosinophil counts which indicates "asthmatic type" inflammation and treat them for a year with mepolizumab. This is a licenced medication for asthma. Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels and is effective at reducing exacerbations in asthmatics. To determine whether mepolizumab may be an effective treatment in people with COPD and "asthmatic type" inflammation participants will have MRI scans before the treatment, after 12 weeks and after a year to see how the drug affects inflammation. The investigators will also compare our measurements with the number of exacerbations people get (measured by diaries), with measures of their quality of life (using a questionnaire), and with ordinary laboratory breathing tests. The investigators are especially interested to know if the reduction in inflammation early on after 12 weeks is associated with fewer exacerbations and better quality of life over the year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment arm (all participants, not randomised) | Experimental | All participants will be treated with mepolizumab, a 100mg dose every 4 weeks for 1 year (13 doses) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mepolizumab 100 MG | Drug | participants will receive 100mg of mepolizumab every 4 weeks for 52 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percentage Ventilated Defect Percent (VDP) | The within subject change in VDP assessed by XeMRI from baseline to 12 weeks of treatment with mepolizumab. Since the protocol was written, the convention has been to report ventilation defect, the percentage of lung that is not ventilated, rather than %VV, the percentage that is ventilated. A decrease in ventilation defect is an improvement in ventilation. | Baseline to 12 weeks of treatment |
| Change in Pulmonary Inflammation | The within participant change in membrane (M)/gas (the ratio of xenon dissolved in the alveolar membrane to gaseous xenon in the airspaces, a measure of alveolar membrane absorption) assessed by XeMRI from baseline to 12 weeks of mepolizumab as an index of pulmonary inflammation. M/gas is a measure of alveolar thickness, which is an index of pulmonary inflammation. An decrease in M/gas indicates reduced inflammation. | From Baseline to 12 weeks of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change in MRI Metrics in Low and High Exacerbation Groups - Longitudinal Relaxation Time (T1) | Comparison of change in MRI metrics (Longitudinal relaxation time (T1)) from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total exacerbations over 52 weeks assessed by EXACT-Pro). Longitudinal relaxation time (T1) is intrinsic MRI relaxation time affected by changes in tissue water content, this measure is expected to increase with inflammation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in MRI Indices of Ventilation - 52 Weeks | Change in MRI indices of ventilation. %VV at 52 weeks compared to baseline, as measured by Xenon MRI scan. An increase in ventilated volume indicates an increase in the area of lung that oxygen can reach. | From Baseline to 52 weeks of treatment |
| Correlation of Changes to Measures of Lung Function and Inflammation (MRI and Physiological) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rod Lawson | Sheffield Teaching Hospitals NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Facility - NGH | Sheffield | S Yorkshire | S5 7AU | United Kingdom |
This is not a randomised controlled trial, so all participants who were confirmed as eligible after the screening visit were allocated to receive the study drug.
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants Who Received the Study Drug (All Eligible Participants) | Participants who received the study drug (All eligible participants) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants completing assessment 1 |
| |||||||||||||
| Participants completing assessment 2 |
| |||||||||||||
| Participants completing assessment 3 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants Completing Assessment 2 | Participants who completed the 12 week MRI assessment visit |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Percentage Ventilated Defect Percent (VDP) | The within subject change in VDP assessed by XeMRI from baseline to 12 weeks of treatment with mepolizumab. Since the protocol was written, the convention has been to report ventilation defect, the percentage of lung that is not ventilated, rather than %VV, the percentage that is ventilated. A decrease in ventilation defect is an improvement in ventilation. | Posted | Mean | Standard Deviation | % change in VDP | Baseline to 12 weeks of treatment |
|
Consent to end of participant involvement. maximum 16months
Definitions as per clinicaltrials.gov definitions
Acute exacerbations of COPD were not included in AE assessment as these were captured as endpoint data
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants Entering the Study | All participants from the point of consent (31) whether or not they received study drug. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemiplegic Migraine | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Lisa Watson | Sheffield Teaching Hospitals | 01142265424 | sth.researchadministration@nhs.net |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 19, 2024 | Dec 18, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C434107 | mepolizumab |
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| From Baseline to 12 weeks of treatment |
| Change in MRI Metrics in Low and High Exacerbation Groups - M0 | Comparison of change in MRI metrics (Proton spin density (M0)) from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total exacerbations over 52 weeks assessed by EXACT-Pro). Proton spin density (M0) is a measure of parenchymal density affected by changes in tissue water content, this measure is expected to increase with inflammation. | From Baseline to 12 weeks of treatment |
Correlation of change in physiological measures and MRI measures of lung function and inflammation at 12 weeks. Correlations were made between the change in 13 lung function measurements and 22 MRI measurements between 0-12 weeks. |
| From Baseline to 12 weeks of treatment |
| Various Correlations of Change of Ventilation, Perfusion and Inflammation Measures | Correlations of change in 4 key physiological and MRI determined measures of ventilation, perfusion and inflammation (47 measures) at 12 weeks from baseline were calculated. | From Baseline to 12 weeks of treatment |
| Overall Impact of Mepolizumab Treatment on HRQoL in COPD (12 Weeks) | Comparison of change of COPD Assessment Test from baseline to 12 weeks within participants compare to changes in measures of lung function by physiology and MRI. | From Baseline to 12 weeks of treatment |
| Overall Impact of Mepolizumab Treatment on HRQoL in COPD (52 Weeks) | Comparison of change of COPD Assessment Test from baseline to 52 weeks within participants compare to changes in measures of lung function by physiology and MRI (36 measures). | From Baseline to 52 weeks of treatment |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | Change in Pulmonary Inflammation | The within participant change in membrane (M)/gas (the ratio of xenon dissolved in the alveolar membrane to gaseous xenon in the airspaces, a measure of alveolar membrane absorption) assessed by XeMRI from baseline to 12 weeks of mepolizumab as an index of pulmonary inflammation. M/gas is a measure of alveolar thickness, which is an index of pulmonary inflammation. An decrease in M/gas indicates reduced inflammation. | There was missing data for 4 participants for this measure. | Posted | Median | Inter-Quartile Range | ratio | From Baseline to 12 weeks of treatment |
|
|
|
| Secondary | Change in MRI Metrics in Low and High Exacerbation Groups - Longitudinal Relaxation Time (T1) | Comparison of change in MRI metrics (Longitudinal relaxation time (T1)) from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total exacerbations over 52 weeks assessed by EXACT-Pro). Longitudinal relaxation time (T1) is intrinsic MRI relaxation time affected by changes in tissue water content, this measure is expected to increase with inflammation. | Moderate and severe exacerbations were counted for the 20 participants who completed the full 52 weeks of the study, of these data was collected for this outcome measure in 17 participants. The two groups were similar in terms of age, sex, smoking status, breathlessness, CAT score, and spirometry. Baseline eosinophil count and FeNO was similar and only differed in exacerbation number. | Posted | Mean | Standard Deviation | ms | From Baseline to 12 weeks of treatment |
|
|
|
| Secondary | Change in MRI Metrics in Low and High Exacerbation Groups - M0 | Comparison of change in MRI metrics (Proton spin density (M0)) from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total exacerbations over 52 weeks assessed by EXACT-Pro). Proton spin density (M0) is a measure of parenchymal density affected by changes in tissue water content, this measure is expected to increase with inflammation. | Moderate and severe exacerbations were counted for the 20 participants who completed the full 52 weeks of the study, data for this outcome measure was collected in 17 participants. The two groups were similar in terms of age, sex, smoking status, breathlessness, CAT score, and spirometry. Baseline eosinophil count and FeNO was similar and only differed in exacerbation number. | Posted | Mean | Standard Deviation | arbitrary units | From Baseline to 12 weeks of treatment |
|
|
|
| Other Pre-specified | Change in MRI Indices of Ventilation - 52 Weeks | Change in MRI indices of ventilation. %VV at 52 weeks compared to baseline, as measured by Xenon MRI scan. An increase in ventilated volume indicates an increase in the area of lung that oxygen can reach. | Posted | Mean | Standard Deviation | % Ventilated lung volume | From Baseline to 52 weeks of treatment |
|
|
|
| Other Pre-specified | Correlation of Changes to Measures of Lung Function and Inflammation (MRI and Physiological) | Correlation of change in physiological measures and MRI measures of lung function and inflammation at 12 weeks. Correlations were made between the change in 13 lung function measurements and 22 MRI measurements between 0-12 weeks. | 25 individuals had usable data for this outcome measure at week 12. 286 correlations were made between physiological measures and MRI measures of lung function | Posted | Number | significant correlations | From Baseline to 12 weeks of treatment | correlations | correlations |
|
|
|
| Other Pre-specified | Various Correlations of Change of Ventilation, Perfusion and Inflammation Measures | Correlations of change in 4 key physiological and MRI determined measures of ventilation, perfusion and inflammation (47 measures) at 12 weeks from baseline were calculated. | 25 participants had usable data at this time point 188 correlations were made between ken physiological measures and MRI determined measures of ventilation, perfusion and inflammation | Posted | Number | significant correlations | From Baseline to 12 weeks of treatment | correlations | correlations |
|
|
|
| Other Pre-specified | Overall Impact of Mepolizumab Treatment on HRQoL in COPD (12 Weeks) | Comparison of change of COPD Assessment Test from baseline to 12 weeks within participants compare to changes in measures of lung function by physiology and MRI. | 25 participants had usable data at this timepoint CAT was correlated with 36 measures of lung function by physiology and MRI. | Posted | Number | significant correlations | From Baseline to 12 weeks of treatment | correlations | correlations |
|
|
|
| Other Pre-specified | Overall Impact of Mepolizumab Treatment on HRQoL in COPD (52 Weeks) | Comparison of change of COPD Assessment Test from baseline to 52 weeks within participants compare to changes in measures of lung function by physiology and MRI (36 measures). | 20 participants had usable data at this timepoint CAT scores were correlated with 36 measures of lung function by physiology and MRI | Posted | Number | significant correlations | From Baseline to 52 weeks of treatment | correlations | correlations |
|
|
|
| 1 |
| 31 |
| 7 |
| 31 |
| 31 |
| 31 |
| Anaphylaxis | Immune system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pyelonephritis | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Benign prostatic hyperplasia (BPH) | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Acute Cholecystitis | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Claustrophobia | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Vaccination site bruising | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cataract operation | Surgical and medical procedures | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
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| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |