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

COPD Clinical Trial

— SUMMER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05138250
• Other study ID #: STH21067
• Status: Recruiting
• Phase: Phase 3
• Start date: May 26, 2022
• Est. completion date: May 2025

Study information

• Verified date: April 2023
• Source: Sheffield Teaching Hospitals NHS Foundation Trust
• Contact: Rod Lawson
• Phone: 01142714278
• Email: rod.lawson[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: May 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COPD
• Inflammation

Intervention

Drug:
• Mepolizumab 100 MG
participants will receive 100mg of mepolizumab every 4 weeks for 52 weeks

Locations

Country	Name	City	State
United Kingdom	Clinical Research Facility - NGH	Sheffield	S Yorkshire

Sponsors (2)

Lead Sponsor	Collaborator
Sheffield Teaching Hospitals NHS Foundation Trust	University of Sheffield

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in MRI indices of ventilation, perfusion and inflammation - 52 weeks	Change in MRI indices of ventilation, perfusion and inflammation (see text) - %VV, CV, RBC/TP, TP/gas, RBC/gas, ADC, LmD, Ve, Ktrans, PBV, PBF, MTT, VQ-intersect, T1, M0 at 52 weeks compared to baseline and 12 weeks	52 weeks
Other	Correlation of changes to measures of lung function and inflammation (MRI and physiological)	Correlation of changes in physiological measures and MRI measures of lung function and inflammation (see text) at 12 weeks	12 weeks
Other	Various correlations of change of ventilation, perfusion and inflammation measures	Change in physiological and MRI determined measures of ventilation, perfusion and inflammation at 12 weeks from baseline will be correlated with; Baseline peripheral blood eosinophil count; Baseline FeNO; Change of peripheral blood eosinophil count from baseline to 12 weeks; Change in FeNO from baseline to 12 weeks. Similar correlation will be carried out for data obtained at 52 weeks rather than 12 weeks.	12 weeks and 52 weeks
Other	Change in MRI metrics in groups with low or high numbers of moderate to severe exacerbations	Comparison of change in MRI metrics from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total moderate to severe exacerbations over 52 weeks assessed by EXACT-Pro)	12 weeks
Other	Overall impact of mepolizumab treatment on HRQoL in COPD	Comparison of change of CAT from baseline to 12 and 52 weeks within participants compare to changes in measures of lung function by physiology and MRI.	12 and 52 weeks
Other	Overall impact of mepolizumab treatment on HRQoL in COPD	Comparison of changes in physiological and MRI derived parameters at 12 weeks in groups with either high and low improvement of CAT at 52 weeks (determined by median split)	12 and 52 weeks
Other	Correlation of PREFUL and DCE MRI measures	PREFUL %VV and PREFUL %PV will be correlated with XeMRI and proton MRI determined measures of lung function at all time points	52 weeks (all timepoints)
Primary	Change in percentage ventilated volume of lung (%VV)	The within subject change in percentage ventilated volume of lung (%VV) assessed by XeMRI from baseline to 12 weeks of treatment with mepolizumab	12 weeks
Primary	Change in alveolar thickness	The within participant change in TP/gas (a measure of alveolar thickness, as an index of pulmonary inflammation) assessed by XeMRI from baseline to 12 weeks of treatment with mepolizumab.	12 weeks
Secondary	Change in MRI metrics in low and high exacerbation groups	Comparison of change in MRI metrics 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)	12 weeks
Secondary	Change in MRI indices of ventilation, perfusion and inflammation - 12 weeks	Change in MRI indices of ventilation, perfusion and inflammation - CV, RBC/TP, RBC/gas, ADC, LmD, Ve, Ktrans, PBV, PBF, MTT, VQ-intersect, T1, M0 from baseline to 12 weeks	12 weeks