Clinical trial NCT04924478: Evaluation of Volatile Organic Compounds in Mepolizumab Therapy
Official title: Evaluation of Volatile Organic Compound Signatures as a Predictive and Therapeutic Response Biomarker for Mepolizumab Therapy in Severe Eosinophilic Asthma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma; Eosinophilic
Keywords: Exhaled Breath
VOC
Mepolizumab
Severe Asthma
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2021-06-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited from University Hospital Southampton (UHS). UHS operates a regional specialist clinical severe asthma service, prescribing biological therapies, including Mepolizumab. Patients will be exclusively recruited from a pool of patients awaiting biological therapies for severe asthma at these centres. Patients are only eligible for Mepolizumab following NICE mandated multidisciplinary team approval reviewing biological eligibility, treatment adherence and satisfaction that other co-morbid conditions have been satisfactorily addressed.

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.

Eligibility criteria: 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 \[Note: Controlled obstructive sleep apnoea (OSA), minor bronchiectasis, asbestos pleural plaques or old (inactive) TB scars are not exclusion criteria\]. Patients where an asthma-COPD overlap is suspected by the investigator are not eligible for inclusion
* 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
* Current smoker or smoked in the past 12 month prior to Visit 1 or any history of e-cigarette use
* Female patients who are pregnant or lactating or planning a family
* Treatment with any of the following prior to Visit 1 or during the study
* Any biologic medicine for asthma or an immunomodulating biologic agent for other conditions in the 6 months prior to Visit 1
* An investigational agent within 30 days of Visit 1 (or five half-lives of the investigational agent, whichever is longer).
* Administration of live attenuated vaccine 30 days prior to Visit 1. Other types of vaccines are allowed.
* Other ongoing immunosuppressive/ immunomodulating therapy \[e.g. methotrexate, ciclosporine, azathioprine\] other than oral corticosteroids for asthma.
* Bronchial thermoplasty conducted within 6 months of Visit 1.
* Patients with helminth infections must be excluded until the infection has been treated
* Known hypersensitivity to Mepolizumab

Primary outcomes:
measure: Response to Mepolizumab
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
measure: Change in Lung physiology with Mepolizumab therapy
timeFrame: 12 months
measure: Change in Immune responses with Mepolizumab therapy
timeFrame: 12 months
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Adnan Azim, MBBS
role: PRINCIPAL_INVESTIGATOR
References: