Exploring Asthma Exacerbations in Mepolizumab Treated Patients

NCT03324230 | Completed

• 1 other identifier: B17/30
• Study Type: observational
• Target: 146
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multicentre, observational study focusing on exacerbation events in patients with severe eosinophilic asthma on Mepolizumab. Mepolizumab is an anti-IL5 (Interleukin 5) monoclonal antibody which blocks the eosinophilic activation pathways associated with decreasing asthma control. The pre-licensing studies have shown that Mepolizumab decreases asthma exacerbation events by approximately 50%, this study seeks to understand the underlying mechanisms of the remaining 50% of exacerbations. The study will enrol patients within GINA classification 4 and 5 who are known to difficult asthma services across four UK sites. Some patients will recently have been commenced on Mepolizumab, whilst others will be commenced on the drug on entry to the study. The patients will have baseline measurements of biomarkers, lung function, sputum analysis and quality of life questionnaires on study entry, after which patients will be asked to contact the clinic at the first signs of worsening asthma symptoms to arrange a clinic visit prior to commencing rescue treatment. They will be clinically assessed with review of peak flow and symptom diaries, measurements taken at baseline will be repeated and a decision on the nature of the exacerbation and treatment required will be made. This is an observational study, all outcomes will be exploratory.

Conditions

Asthma Brittle

Keywords

Monoclonal antibody; Mepolizumab; Eosinophil

Outcome Measures

Primary Outcomes (10)

• Number of asthma exacerbations requiring administration of corticosteroids

  Mepolizumab is considered to be a steroid sparing drug resulting in a reduced number of asthma exacerbations. Patients will be reviewed when asthma symptoms worsen to assess the cause of loss of asthma control and ascertain if the exacerbations requires administration of corticosteroids.

  Throughout study completion, an average of 2 years

• Forced Expiratory Volume in 1 second

  Spirometry to assess Forced Expiratory Volume in 1 (FEV1) second will be performed at baseline entry to the study and on worsening of asthma symptoms. Spirometry will performed in keeping with the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines.

  Throughout study completion, an average of 2 years

• Forced vital capacity

  Spirometry to assess Forced Vital Capacity (FVC) will be undertaken at baseline and at worsening of asthma symptoms. Spirometry will performed in keeping with the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines.

  Throughout study completion, an average of 2 years

• Fractional expired nitric oxide (feno)

  Feno will be measured at baseline and during unscheduled visits to assess airway inflammation.

  Throughout study completion, an average of 2 years

• Mini-AQLQ

  The mini-Asthma Quality of Life Questionnaire (mini-AQLQ) will be used throughout the study to assess effect of asthma on the subject's quality of life.

  Throughout study completion, an average of 2 years

• Asthma control questionnaire (ACQ)

  The Asthma control questionnaire (ACQ) will be used throughout the study to assess effect of asthma on the subject's quality of life.

  Throughout study completion, an average of 2 years

• Saint George's Respiratory Questionnaire (SGRQ).

  The Saint George's Respiratory Questionnaire (SGRQ)will be used throughout the study to assess effect of asthma on the subject's quality of life.

  Throughout study completion, an average of 2 years

• Eosinophils

  Complete blood count with breakdown of individual cell counts will be measured at baseline and worsening of asthma symptoms

  Throughout study completion, an average of 2 years

• C reactive protein

  Serum C reactive protein will be measured at baseline and worsening of asthma symptoms.

  Throughout study completion, an average of 2 years

• Sputum analysis

  The breakdown of the sputum white cell count will be analysed to assess for eosinophilia and neutrophilia.

  Throughout study completion, an average of 2 years

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients known to Difficult Asthma services within the NHS, who are eligible for Mepolizumab treatment as per NICE guidelines.

You may qualify if:

• Age ≥ 18 and ≤ 80 years at Visit 1
• Able and willing to provide written informed consent and to comply with the study protocol including being able to contact the clinical center and to attend for assessment during a symptomatic deterioration
• Severe asthma despite confirmed after assessment by an asthma specialist
• Diagnosed with asthma at least 12 months prior to screening

You may not qualify if:

• Acute exacerbation requiring oral corticosteroids in 4 weeks before screening.
• 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
• 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 5 half-lives of the investigational agent, whichever is longer)
• Female subjects who are pregnant or lactating (excluded as candidates for Mepolizumab in clinic prior to study)

Sponsors & Collaborators

• Queen's University, Belfast: lead
• RASP (Refractory Asthma Stratification Programme): collaborator
• Medical Research Council: collaborator
• University of Oxford: collaborator
• University of Leicester: collaborator
• NHS Greater Glasgow and Clyde: collaborator
• Belfast Health and Social Care Trust: collaborator

Study Sites (4)

Queen's University Belfast

Belfast, County Antrim, BT7 1NN, United Kingdom

Location

Leicester Biomedical Research Centre

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Gartnavel General Hospital, Greater Glasgow and Clyde NHS Trust

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Oxford University

Oxford, United Kingdom

Location

Related Publications (7)

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  PMID: 9309994 BACKGROUND

• Barnes PJ, Jonsson B, Klim JB. The costs of asthma. Eur Respir J. 1996 Apr;9(4):636-42. doi: 10.1183/09031936.96.09040636.

  PMID: 8726924 BACKGROUND

• Sweeney J, Brightling CE, Menzies-Gow A, Niven R, Patterson CC, Heaney LG; British Thoracic Society Difficult Asthma Network. Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry. Thorax. 2012 Aug;67(8):754-6. doi: 10.1136/thoraxjnl-2012-201869. Epub 2012 May 11.

  PMID: 22581823 BACKGROUND

• Ahmad F, Roman J. Treating refractory asthma with antibodies against IL-5: is it ready for prime time? Expert Rev Respir Med. 2009 Jun;3(3):227-30. doi: 10.1586/ers.09.22.

  PMID: 20477317 BACKGROUND

• Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.

  PMID: 22901886 BACKGROUND

• Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27.

  PMID: 22743675 BACKGROUND

• McDowell PJ, Diver S, Yang F, Borg C, Busby J, Brown V, Shrimanker R, Cox C, Brightling CE, Chaudhuri R, Pavord ID, Heaney LG; Medical Research Council: Refractory Asthma Stratification Programme (RASP-UK Consortium). The inflammatory profile of exacerbations in patients with severe refractory eosinophilic asthma receiving mepolizumab (the MEX study): a prospective observational study. Lancet Respir Med. 2021 Oct;9(10):1174-1184. doi: 10.1016/S2213-2600(21)00004-7. Epub 2021 May 7.

  PMID: 33971168 DERIVED

Related Links

• 2017 GINA Report, Global Strategy for Asthma Management and Prevention

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, sputum, urine.

Study Officials

• Liam Heaney, MB Bch BaO

  Queen's University, Belfast

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: October 27, 2017
• Study Start: December 1, 2017
• Primary Completion: June 29, 2019
• Study Completion: June 29, 2019
• Last Updated: July 10, 2019

Record last verified: 2019-07

Locations

GB (4)