Evaluation of Volatile Organic Compounds in Mepolizumab Therapy

Asthma; Eosinophilic Clinical Trial

— EVOC4M  

Official title:

Evaluation of Volatile Organic Compound Signatures as a Predictive and Therapeutic Response Biomarker for Mepolizumab Therapy in Severe Eosinophilic Asthma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04924478
• Other study ID #: RHM MED1746
• Status: Not yet recruiting
• Start date: July 2021
• Est. completion date: December 2022

Study information

• Verified date: June 2021
• Source: University Hospital Southampton NHS Foundation Trust
• Contact: Adnan Azim
• Phone: 02381204479
• Email: a.azim[@]soton.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Asthma; Eosinophilic
• Pulmonary Eosinophilia

Intervention

Biological:
• Mepolizumab
Patients will be receiving this treatment as part of their standard clinical care

Locations

Country	Name	City	State
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Southampton NHS Foundation Trust	GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Lung physiology with Mepolizumab therapy	measured by Impulse Oscillometry	12 months
Other	Change in Immune responses with Mepolizumab therapy	measured by whole blood gene expression profiling	12 months
Primary	Response to Mepolizumab	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	12 months