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

NCT05138250 | Completed Phase 3 Results

• 1 other identifier: STH21067
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COPD

Keywords

MRI, eosinophil, exacerbation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Change in MRI Metrics in Low and High Exacerbation Groups - Longitudinal Relaxation Time (T1)

  From Baseline to 12 weeks of treatment

• Change in MRI Metrics in Low and High Exacerbation Groups - M0

  From Baseline to 12 weeks of treatment

Other Outcomes (5)

• Change in MRI Indices of Ventilation - 52 Weeks

  From Baseline to 52 weeks of treatment

• Correlation of Changes to Measures of Lung Function and Inflammation (MRI and Physiological)

  From Baseline to 12 weeks of treatment

• Various Correlations of Change of Ventilation, Perfusion and Inflammation Measures

  From Baseline to 12 weeks of treatment

Study Arms (1)

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)

Drug: Mepolizumab 100 MG

Interventions

Mepolizumab 100 MG DRUG

participants will receive 100mg of mepolizumab every 4 weeks for 52 weeks

Treatment arm (all participants, not randomised)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator

Study Sites (1)

Clinical Research Facility - NGH

Sheffield, S Yorkshire, S5 7AU, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Lisa Watson
• Organization: Sheffield Teaching Hospitals

sth.researchadministration@nhs.net

01142265424

Study Officials

• Rod Lawson

  Sheffield Teaching Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: November 30, 2021
• Study Start: May 8, 2022
• Primary Completion: May 8, 2025
• Study Completion: May 8, 2025
• Last Updated: May 7, 2026
• Results First Posted: May 7, 2026

Record last verified: 2026-05

Locations

GB (1)