Inflammation Following Mepolizumab and Oral Corticosteroids in Asthma

Asthma Clinical Trial

— MAPLE  

Official title:

Persistence of Inflammation and Study of T2 Pathways Following Inhibition of InterLeukin-5 With Mepolizumab in Severe Eosinophilic Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03610685
• Other study ID #: GN17RM707
• Status: Completed
• Phase: Phase 4
• Start date: October 19, 2018
• Est. completion date: January 7, 2020

Study information

• Verified date: March 2020
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the project is to study the persistence of inflammation after addition of an interleukin-5 (IL-5) blocker in severe eosinophilic asthma as a study of untreated pathways in these patients.

Description:

Mepolizumab, a humanized monoclonal antibody (mAb) antagonizes IL-5 and through a selective inhibition of eosinophilic inflammation, reduces the number of eosinophils in sputum and blood, leading to a reduction in asthma exacerbations and a need for systemic glucocorticoids. Once this therapy has been initiated for severe eosinophilic asthma, the additional role of oral corticosteroids is questionable as their main target is reduction of eosinophils and hence responsiveness to oral corticosteroids in patients in a stable state of asthma may reduce.

Using two weeks of high dose prednisolone versus placebo in a crossover design after 12 weeks of mepolizumab therapy will allow an understanding of the pathways that remain steroid responsive following IL-5 suppression.

This is an exploratory study with no single primary end point. The objective of the study is to assess the change in airway inflammation following oral corticosteroids versus placebo and the airway inflammation while on mepolizumab in stable state of asthma.

Note: Mepolizumab is not an intervention in this study; it is initiated as part of usual NHS care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 7, 2020
• Est. primary completion date: January 7, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age = 18 and = 80 years at consent.

• Able and willing to provide written informed consent and to comply with the study protocol.

• Severe asthma diagnosis confirmed after assessment by an asthma specialist.

• Suitable for mepolizumab as per NICE/SMC Clinical Guidelines.

Exclusion Criteria:

• Maintenance oral corticosteroid treatment within the past four weeks.

• Acute exacerbation requiring oral corticosteroids in the four weeks prior to consent.

• Other clinically significant medical disease or uncontrolled concomitant disease despite treatment that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study or be significantly worsened by oral corticosteroids.

• History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.

• Treatment with an investigational agent within 30 days of Visit 1 (or five half-lives of the investigational agent, whichever is longer).

• Women of child-bearing potential who are pregnant, lactating, planning pregnancy during the study period or are unwilling to use a highly effective form of contraception.

• Known hypersensitivity to prednisolone or its excipients.

• Previous psychiatric adverse reactions to steroid therapy in the past.

• Concomitant medication with systemic anti-fungals such as ketoconazole, retinoids, tetracycline, other systemic immunosuppressants e.g. ciclosporin, azathioprine, mycophenolate and live vaccines during the crossover trial.

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Drug:
• Prednisolone
Given daily for 2 weeks
• Placebo oral capsule
Given daily for 2 weeks

Locations

Country	Name	City	State
United Kingdom	Asthma and copd research centre	Glasgow

Sponsors (2)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	Queen's University, Belfast

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in asthma control and quality of life questionnaires	Asthma control questionnaire includes 5 questions related to asthma control. Each question is scored from 0 to 6 with the highest number representing poorer outcome / asthma control.; Asthma quality of life questionnaire includes 32 questions related to quality of life. Each question is scored from 1 to 7 with the highest number representing better outcome / quality of life.	Through study completion, an average 20 weeks.
Other	Change in visual asthma symptom scores	Symptoms visual analogue scale asks 3 questions related to asthma control. A	Through study completion, an average 20 weeks
Other	Oscillometry	For small airway function to correlate with inflammation	Through study completion, an average 20 weeks
Primary	Change in exhaled nitric oxide measured in parts per billion	Measured at study visits using a Niox machine.	Through study completion, an average 20 weeks.
Primary	Change in sputum differential cell counts measured in absolute cell count.	Induced sputum	Through study completion, an average 20 weeks