Asthma; Eosinophilic
Conditions
Keywords
Exhaled Breath, VOC, Mepolizumab, Severe Asthma
Brief summary
This study will recruit patients who are being prescribed Mepolizumab as part of their standard clinical care for the treatment of severe eosinophilic asthma. Over the course of their treatment, research data (questionnaires) and research samples (blood, breath and urine) will be collected in parallel to standard clinical measurements. The data and samples will be investigated to help better understand how Mepolizumab works, why it doesn't work in certain patients and why it works very well in others. This will help prescribers better identify patients that will benefit from Mepolizumab.
Detailed description
EVOC4M is a prospective observational study investigating Mepolizumab in the treatment of severe eosinophilic asthma. This study will recruit patients receiving Mepolizumab as part of their standard clinical care in an NHS commissioned Specialised Adult Severe Asthma Service. Over the course of their treatment, research data (questionnaires) and research samples (blood, breath and urine) will be collected in parallel to standard clinical measurements. Clinical studies have demonstrated blood eosinophil levels to be predictive of the magnitude of the impact of Mepolizumab in reducing severe disease exacerbations but it is appreciated that there are still treatment failures despite this selection criteria. Clinical decision and policymaking are increasingly concerned by the health economic implications of these high-cost therapies and so clinical biomarkers are now being sought for theragnostics: prediction of treatment response The study will try to identify biomarkers that will can discriminate between those that respond to Mepolizumab (responders) and those that do not (non-responders). This will improve our understanding of how Mepolizumab works. In particular, the investigators are interested in exhaled volatile organic compounds (VOCs), which are measured in exhaled breath samples. Exhaled breath is safe and easy to collect and has direct contact with the organ of interest, the airways. A VOC biomarker that predicts Mepolizumab success may translate to clinical practice.
Interventions
BIOLOGICALMepolizumab
Patients will be receiving this treatment as part of their standard clinical care
Sponsors
GlaxoSmithKline
University Hospital Southampton NHS Foundation Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 and ≤ 80 years at Visit 1 * Able and willing to provide written informed consent and to comply with the study protocol * Severe asthma confirmed after assessment by an asthma physician, requiring treatment with high dose inhaled corticosteroids (ICS) as per BTS criteria \[≥1000 micrograms fluticasone propionate equivalent\] and ≥ 1 additional drug for asthma \[e.g. long acting beta2 agonist (LABA), leukotriene receptor antagonist (LTRA) such as montelukast, theophylline, long acting muscarinic antagonist (LAMA) such as tiotropium) at screening \[participants may be included with a lower dose of current ICS at the discretion of the investigator if previous high ICS dose had led to side effects\] * Adherent with background asthma medication in the opinion of the local MDT * Assessed and treatment optimized for any significant asthma-related co-morbidities in the opinion of the local MDT * Considered suitable by an asthma specialist for treatment with a monoclonal antibody to block the Interleukin-5 pathway as per local practice, in accordance with NICE TA 431 * a recorded blood eosinophil count ≥0.3 x 109/L within the past year * history of either ≥ 4 asthma exacerbations requiring high dose oral corticosteroids (exacerbations of asthma in the past year will be defined as worsening of asthma symptoms leading to treatment with prednisolone ≥30 mg oral corticosteroids for ≥3 days as defined by the ERS/ATS Task Force) OR * has had continuous oral corticosteroids of at least the equivalent of prednisolone 5 mg per day over the previous 6 months
Exclusion criteria
* Acute exacerbation requiring high dose oral corticosteroids in the 4 weeks prior to Visit 1. Such patients would be re-assessed when 4 weeks clear of the oral corticosteroid course for re-screening. * Long term systemic antibiotic or antifungal therapy * Other clinically significant medical disease (including malignancy or immunodeficiency requiring treatment) or uncontrolled concomitant disease that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study * Active lung disease other than asthma \[Note: Controlled obstructive sleep apnoea (OSA), minor bronchiectasis, asbestos pleural plaques or old (inactive) TB scars are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Mepolizumab | 12 months | defined as positive if Clinical multidisciplinary team decision that patient has had a positive response OR \>50% reduction in number of exacerbations per year OR 0.5 point reduction in ACQ score |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Lung physiology with Mepolizumab therapy | 12 months | measured by Impulse Oscillometry |
| Change in Immune responses with Mepolizumab therapy | 12 months | measured by whole blood gene expression profiling |
Countries
United Kingdom
Contacts
Primary ContactAdnan Azim
Backup ContactMatt Harvey
Outcome results
None listed