A Pilot Study of the Use of 129Xe and 1H MRI to Measure the Modulation of Eosinophil-Related Inflammation by Mepolizumab In COPD (SUMMER)

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Mepolizumab 100 MG

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • S Yorkshire
    • Sheffield, S Yorkshire, United Kingdom, S5 7AU
      • Clinical Research Facility - NGH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of COPD as determined by a post bronchodilator FEV1/FVC <70% and an FEV1 of between 20 and 80% at screening visit
• Treatment with inhaled triple therapy (licensed combination of long acting beta 2 agonist, long acting anti-muscarinic and corticosteroid) at constant dose for at least 12 weeks before screening visit. Treatment with roflumilast, theophyillines and macrolides will be permitted so long as they were introduced at stable dose > 12 weeks prior to screening visit. (If maintenance drug dosing has not been with stable dosages for 12 weeks the screening visit may be rescheduled until this is achieved: see sections 7.3 and 7.10)
• At least 2 acute exacerbations of COPD (AECOPD) requiring treatment with oral steroids and/or antibiotics in the last 12 months, or 1 acute AECOPD requiring hospital admission in the last 12 months.
• At least one eosinophil count of >0.3 cells·μL-1 in the 12 months prior to screening
• Age over 18 years

Exclusion Criteria:

• Contraindication to MRI scanning, including Gadovist (ie hypersensitivity or poor renal function; see below); this includes claustrophobia and musculoskeletal difficulties, this information is collected on the UoS MRI unit screening form.
• Inability to give informed consent or comply with study procedures
• Hypersensitivity to mepolizumab or its excipients
• Untreated helminthic infection
• Exacerbation of COPD requiring treatment with oral steroids and/or antibiotics within 4 weeks of screening. A repeat screening visit may be scheduled in order to achieve this criterion. The participant will be required to successfully complete all screening procedures at the rescheduled visit, including that for exacerbation-free stability.
• SpO2 <90% on room air at screening
• Clear history of childhood and/or current asthma
• Past history of lung surgery
• Other significant lung disease
• Long term oral steroid treatment
• eGFR < 30 ml/min/1.73 m2 at screening
• NYHA class 3 or 4, where the functional limitation from heart disease is greater than that from COPD, or uncompensated heart failure
• Chronic liver disease (Any elevation of ALT above twice the upper limit of normal at screening. Lower levels of abnormality are permitted after investigator review if felt not to compromise safety)
• Malignancy unless treated and disease free for 5 years
• Conditions causing significant immunosuppression
• Active infection with blood borne viruses (including hepatitis A and B and HIV)
• Other significant medical condition compromising participant safety or fidelity of study.
• Pregnant or breast feeding
• Of childbearing potential and not willing to use highly effective methods of contraception during the course of the study and for 100 days post last dose of mepolizumab.
• Participants who have received an investigational drug within 30 days of first dose, or within 5 drug half-lives of the investigational drug, whichever is longer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm (all participants, not randomised); All participants will be treated with mepolizumab, a 100mg dose every 4 weeks for 1 year (13 doses)	Drug: Mepolizumab 100 MG; participants will receive 100mg of mepolizumab every 4 weeks for 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Other Outcome Measures

Outcome Measure	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)	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

Collaborators and Investigators

• Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: University of Sheffield
• Investigators: Principal Investigator: Rod Lawson, Sheffield Teaching Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2022
• Primary Completion (Actual): May 8, 2025
• Study Completion (Actual): May 8, 2025

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MRI, eosinophil, exacerbation
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; mepolizumab
• Other Study ID Numbers: STH21067

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No