Residual Exacerbations With Mepolizumab

Study Overview
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Brief Summary
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This will be a two-year prospective study to characterize the nature of the remaining asthma exacerbations in patients treated with mepolizumab. Participants will be assessed every six months from pre- until two years of treatment in addition to whenever they experience an exacerbation of asthma during the study period. During these visits, various clinical, physiological and inflammatory outcomes will be assessed.

Detailed Description
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Before initiation of mepolizumab, a recording of patient's demographics, clinical, physiological and inflammatory features will be recorded. All subjects will be reassessed for the above measures at 6, 12, 18 and 24 months. In addition to the above visits, patients will be assessed every time they experience either moderate or severe exacerbation of asthma over the treatment period. Based on the percentage of sputum eosinophils and neutrophils, the type of inflammatory exacerbation will be determined

Official Title
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Type and Mechanisms of Residual Asthma Exacerbations in Patients Treated With Mepolizumab

Conditions
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Asthma

Intervention / Treatment
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* Drug: Mepolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a proven diagnosis of severe asthma as defined by the Canadian Thoracic Society Eligible for mepolizumab treatment Able and willing to sign the informed consent form Exclusion Criteria: Any respiratory disease apart from asthma Confounding comorbidities sur as eosinophilic granulomatosis with polyangiitis (EGPA) or hypereosinophilic syndrome

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study population<br>Subjects with severe asthma treated with mepolizumab | Drug: Mepolizumab<br>* 100 mg subcutaneous injections every four weeks<br>* Other names: nucala;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of eosinophilic vs non-eosinophilic remaining exacerbation during the treatment period | Eosinophilic exacerbation defined as >=3% sputum eosinophils. Ratio of eosinophilic vs non eosinophilic asthma exacerbation | Between baseline and month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in asthma control on the Asthma Control Questionnaire (ACQ-5) at 24 months | The ACQ-5 is a validated, self-reported questionnaire assessing asthma control over the last week. Possible scores range from 0 (complete control) to 5 (no control). Change = (Month 24 score - baseline score) | Baseline and month 24 | 
| Change from baseline in post-bronchodilator forced expiratory volume in one second (FEV1) at 24 months | Value of FEV1 measured after inhalation of 400ug of salbutamol. Recorded in Li. (Month 24 FEV1 value - baseline FEV1 value) | Baseline and month 24 | 
| Change from baseline in post-bronchodilator FEV1/forced vital capacity (FVC) ratio at 24 months | Value of FEV1/FVC measured after inhalation of 400 ug of salbutamol. (Month 24 value - baseline value) | Baseline and month 24 | 
| Change from baseline in fraction of exhaled nitric oxide (FeNO) levels at 24 months | Recorded in ppb using the mean of two reproducible measurements. (Month 24 value - baseline value) | Baseline and month 24 | 
| Change from baseline in percentage of sputum eosinophils at 24 months | Determined from induced sputum analysis. (Month 24 sputum eosinophil percentages - baseline sputum eosinophil percentages) | Baseline and month 24 | 
| Change from baseline in percentage of sputum neutrophils | Determined from induced sputum analysis. (Month 24 sputum neutrophil percentages - baseline sputum neutrophil percentages). | Baseline and month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exacerbation, inflammation, monoclonal antibody