Ignite Creation Date:
2024-05-06 @ 10:40 AM
Last Modification Date:
2024-10-26 @ 12:34 PM
Study NCT ID:
NCT03324230
Status:
COMPLETED
Last Update Posted:
2019-07-10
First Post:
2017-09-26
Brief Title:
Exploring Asthma Exacerbations in Mepolizumab Treated Patients
Sponsor:
Queens University Belfast
Organization:
Queens University Belfast
Study Overview
Official Title:
Exacerbation Profile in Patients on Mepolizumab for Severe Refractory Eosinophilic Asthma- an Exploratory Study
Status:
COMPLETED
Status Verified Date:
2019-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
Background
Around 15 of the United Kingdom UK have asthma of these 10-20 have asthma which is difficult to control using current therapies and with high levels of morbidity resulting These patients consume 50-60 of the UK healthcare costs of asthma and as such there is much interest in developing novel treatments for this group
The heterogeneity of inflammatory pathways underlying asthma are of great interest with development of biomarkers useful for phenotyping asthmatic patients and allowing more accurate assessment of their response to treatment Traditionally oral corticosteroids are used in eosinophilic T2-high asthmatic patients with good therapeutic effect however there are a group of T2-high patients who have refractory type-2 cytokine driven inflammation and airway eosinophilia despite oral corticosteroids As such there are several novel biological agents being engineered to block type 2 cytokine pathways including antagonists to IL5 IL13 and IL4 Interleukin 5 13 4
Mepolizumab is a humanised monoclonal antibody against IL5 Through a selective inhibition of eosinophilic inflammation the agent reduces the number of eosinophils in sputum and blood with important clinical outcomes such as a reduction of asthma exacerbations and a need for systemic glucocorticoids The pre-licencing clinical trials have shown that selective inhibition of IL5 and presumptive removal of eosinophils reduces exacerbations by 50 but while this is a significant reduction patients with severe asthma continue to have severe exacerbations requiring systemic corticosteroid administration
Therefore the point of interest is eliciting the inflammatory phenotype and physiological characteristics of the remaining 50 of exacerbations and ascertaining whether systemic corticosteroids have a role when the IL-5 pathway has been blocked by Mepolizumab
Purpose Aim This is an observational study designed to phenotype exacerbations or worsening asthma control when participants are established on Mepolizumab The study will look for changes in lung function biomarkers and patient symptoms scores
The hypothesis is as follows In patients with severe refractory eosinophilic asthma who have been established on mepolizumab
- increased asthma symptoms exacerbations will have no evidence of airway eosinophilia and will be clinically mild events associated with small reductions in lung function which may not require rescue oral corticosteroids
Outline plan of investigation This will be an open observational multi-centre cohort study in participants with severe asthma Global Initiative for Asthma GINA Steps 4 and 5 classification of asthma severity who are initiated on Mepolizumab in line with the NICESMC National institute foe Health and Care Excellence Clinical Guidelines
The study is exploratory and will assess deteriorations in asthma control to characterise the clinical severity of each exacerbation and the airway and systemic inflammatory phenotype associated with these events Clinical assessment and management of each exacerbation will be in line with standard clinical guidelines SIGN 153 Scottish Intercollegiate Guidelines Network British Guideline on the Management of Asthma September 2016
The study design incorporates a proportion of participants already established on Mepolizumab as well as participants who will be commenced on Mepolizumab on entry to the study A baseline assessment of medical history clinical examination lung function and sputumbloodurine for analysis will be undertaken along with quality of life questionnaires Those newly started on Mepolizumab will be assessed in a similar manner 3 months into the study
Subjects will be given an electronic peak flow recorder symptoms diary and action plan for change in baseline symptoms Participants will be asked to contact the clinic when they feel there has been a decline in asthma control and before they take rescue treatment a clinic visit will be arranged At this visit all participants will have full medical assessment and clinical management based on detailed medical history clinical findings and lung function measurement Blood will be taken as part of this clinical assessment as outlined in the schedule of study procedures including biobanking of samples for whole blood gene expression serum plasma sputum and urine These samples will be stored for validation of additional biomarkers aligned with the RASP-UK Refractory Asthma Stratification Programme-UK biomarker corticosteroid optimisation study
Number in study
This is a study will take place across 4 NHS sites within the UK namely Belfast Glasgow Oxford and Leicester
The study design incorporates a proportion of participants already established on Mepolizumab and also participants starting on Mepolizumab allowing recruitment of up to 150 participants in a 6 - 9 month window all sites have large numbers of patients on the waiting list for the drug Assuming a conservative 07 exacerbations per patient per year on mepolizumab ca 160 events in an 18 month period and a minimum rate of attendance of 65 this is 102 observed episodes The study will be terminated when 100 clinical assessments at exacerbation in total have been completed across all sites for participants on Mepolizumab prior to initiation of rescue treatment The expected duration of study per participant is 24 months
Around 15 of the United Kingdom UK have asthma of these 10-20 have asthma which is difficult to control using current therapies and with high levels of morbidity resulting These patients consume 50-60 of the UK healthcare costs of asthma and as such there is much interest in developing novel treatments for this group
The heterogeneity of inflammatory pathways underlying asthma are of great interest with development of biomarkers useful for phenotyping asthmatic patients and allowing more accurate assessment of their response to treatment Traditionally oral corticosteroids are used in eosinophilic T2-high asthmatic patients with good therapeutic effect however there are a group of T2-high patients who have refractory type-2 cytokine driven inflammation and airway eosinophilia despite oral corticosteroids As such there are several novel biological agents being engineered to block type 2 cytokine pathways including antagonists to IL5 IL13 and IL4 Interleukin 5 13 4
Mepolizumab is a humanised monoclonal antibody against IL5 Through a selective inhibition of eosinophilic inflammation the agent reduces the number of eosinophils in sputum and blood with important clinical outcomes such as a reduction of asthma exacerbations and a need for systemic glucocorticoids The pre-licencing clinical trials have shown that selective inhibition of IL5 and presumptive removal of eosinophils reduces exacerbations by 50 but while this is a significant reduction patients with severe asthma continue to have severe exacerbations requiring systemic corticosteroid administration
Therefore the point of interest is eliciting the inflammatory phenotype and physiological characteristics of the remaining 50 of exacerbations and ascertaining whether systemic corticosteroids have a role when the IL-5 pathway has been blocked by Mepolizumab
Purpose Aim This is an observational study designed to phenotype exacerbations or worsening asthma control when participants are established on Mepolizumab The study will look for changes in lung function biomarkers and patient symptoms scores
The hypothesis is as follows In patients with severe refractory eosinophilic asthma who have been established on mepolizumab
- increased asthma symptoms exacerbations will have no evidence of airway eosinophilia and will be clinically mild events associated with small reductions in lung function which may not require rescue oral corticosteroids
Outline plan of investigation This will be an open observational multi-centre cohort study in participants with severe asthma Global Initiative for Asthma GINA Steps 4 and 5 classification of asthma severity who are initiated on Mepolizumab in line with the NICESMC National institute foe Health and Care Excellence Clinical Guidelines
The study is exploratory and will assess deteriorations in asthma control to characterise the clinical severity of each exacerbation and the airway and systemic inflammatory phenotype associated with these events Clinical assessment and management of each exacerbation will be in line with standard clinical guidelines SIGN 153 Scottish Intercollegiate Guidelines Network British Guideline on the Management of Asthma September 2016
The study design incorporates a proportion of participants already established on Mepolizumab as well as participants who will be commenced on Mepolizumab on entry to the study A baseline assessment of medical history clinical examination lung function and sputumbloodurine for analysis will be undertaken along with quality of life questionnaires Those newly started on Mepolizumab will be assessed in a similar manner 3 months into the study
Subjects will be given an electronic peak flow recorder symptoms diary and action plan for change in baseline symptoms Participants will be asked to contact the clinic when they feel there has been a decline in asthma control and before they take rescue treatment a clinic visit will be arranged At this visit all participants will have full medical assessment and clinical management based on detailed medical history clinical findings and lung function measurement Blood will be taken as part of this clinical assessment as outlined in the schedule of study procedures including biobanking of samples for whole blood gene expression serum plasma sputum and urine These samples will be stored for validation of additional biomarkers aligned with the RASP-UK Refractory Asthma Stratification Programme-UK biomarker corticosteroid optimisation study
Number in study
This is a study will take place across 4 NHS sites within the UK namely Belfast Glasgow Oxford and Leicester
The study design incorporates a proportion of participants already established on Mepolizumab and also participants starting on Mepolizumab allowing recruitment of up to 150 participants in a 6 - 9 month window all sites have large numbers of patients on the waiting list for the drug Assuming a conservative 07 exacerbations per patient per year on mepolizumab ca 160 events in an 18 month period and a minimum rate of attendance of 65 this is 102 observed episodes The study will be terminated when 100 clinical assessments at exacerbation in total have been completed across all sites for participants on Mepolizumab prior to initiation of rescue treatment The expected duration of study per participant is 24 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None