Inflammation Following Mepolizumab and Oral Corticosteroids in Asthma (MAPLE)

March 4, 2020 updated by: NHS Greater Glasgow and Clyde

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Asthma and copd research centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Participants will be given 2 weeks of placebo treatment. The placebo capsules will be taken once a day orally. The daily dose of placebo treatment will match the Prednisone dose for each participant.
Drug: Placebo oral capsule
Given daily for 2 weeks
Other Names:
  • Placebo
Active Comparator: Prednisolone
Participants will be given 2 weeks of prednisolone treatment. This is administered orally once a day. The daily dose is calculated according to 0.5mg/kg with a maximum dose of 40mg per day.
Drug: Prednisolone
Given daily for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in exhaled nitric oxide measured in parts per billion
Time Frame: Through study completion, an average 20 weeks.
Measured at study visits using a Niox machine.
Through study completion, an average 20 weeks.
Change in sputum differential cell counts measured in absolute cell count.
Time Frame: Through study completion, an average 20 weeks
Induced sputum
Through study completion, an average 20 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in asthma control and quality of life questionnaires
Time Frame: Through study completion, an average 20 weeks.

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.
Change in visual asthma symptom scores
Time Frame: Through study completion, an average 20 weeks
Symptoms visual analogue scale asks 3 questions related to asthma control. A
Through study completion, an average 20 weeks
Oscillometry
Time Frame: Through study completion, an average 20 weeks
For small airway function to correlate with inflammation
Through study completion, an average 20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

Queen's University, Belfast

Investigators

  • Principal Investigator: Rekha Chaudhuri, MD, NHS Greater Glasgow and Clyde

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2018

Primary Completion (Actual)

January 7, 2020

Study Completion (Actual)

January 7, 2020

Study Registration Dates

First Submitted

March 27, 2018

First Submitted That Met QC Criteria

July 25, 2018

First Posted (Actual)

August 1, 2018

Study Record Updates

Last Update Posted (Actual)

March 6, 2020

Last Update Submitted That Met QC Criteria

March 4, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN17RM707

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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