Asthma
Conditions
Keywords
benralizumab, exacerbation, eosinophilic
Brief summary
This is an exploratory study, the focus of which is to understand the nature of asthma exacerbations that occur despite open label benralizumab therapy in severe eosinophilic asthma.
Detailed description
A phase IV, open-label, prospective, multi-centre cohort study in patients with severe eosinophilic asthma (Global Initiative for Asthma \[GINA\] steps 4 and 5 classification of asthma severity) who will be treated with benralizumab injections. The study is exploratory and will assess deteriorations in asthma control (exacerbations) 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. 150 participants will be recruited and receive treatment for either 56 or 80 weeks.
Interventions
DRUGBenralizumab
subcutaneous injection
Sponsors
University of Glasgow
AstraZeneca
Queen's University, Belfast
Bosch Healthcare Solutions GmbH
InHealthcare
University of Leicester
University of Plymouth
Vitalograph
NHS Greater Glasgow and Clyde
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* able and willing to provide written informed consent and to comply with the study protocol, including being able to attend for assessment during a symptomatic deterioration * severe asthma confirmed after assessment by an asthma specialist, requiring treatment with high dose inhaled corticosteroids (ICS) as per BTS criteria \[\>1000 fluticasone proportionate equivalent\] and \>1 additional drug for asthma (e.g. long acting beta 2 antagonist (LABA)/leukotriene receptor antagonist/theophylline/long acting muscarinic antagonist) 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 investigator \[adherence assessments as per local practice\] * Assessed and treatment optimised for any significant asthma-related co-morbidities * Considered suitable by an asthma specialist for treatment with a monoclonal antibody to block the Interleukin-5 pathway as per local practice. Participants will have: a) recorded blood eosinophil count ≥0.3 x 109/L within the past year along with a history of either ≥4 asthma exacerbations requiring high dose oral corticosteroids\* and/or maintenance systemic corticosteroids equivalent to prednisolone ≥5 mg/day for 6 months or longer OR b) recorded blood eosinophil count ≥0.4 x 109/L within the past year along with a history of ≥ 3 asthma exacerbations requiring high dose oral corticosteroids\* * \[Exacerbations of asthma in the past year will be defined as worsening of asthma symptoms leading to treatment with prednisolone ≥30 mg oral corticosteroids for ≥3 days or an increase ≥ 10mg in oral corticosteroids for at least 3 days for patients on maintenance oral steroids\] as defined by the ERS/ATS Task Force
Exclusion criteria
* Acute exacerbation requiring high dose oral corticosteroids in the 2 weeks prior to Visit 1 or during the screening period. Such patients would be re-assessed after 2 weeks for re-screening. * Other clinically significant medical disease 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. * 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. * Female patients who are pregnant or lactating or planning a family * 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 |
|---|---|
| Fall in lung function, as measured by FEV1, during a clinical deterioration whilst on benralizumab. | up to 56 or 80 weeks |
| Change in asthma symptom scores during a clinical deterioration whilst on benralizumab. | up to 56 or 80 weeks |
| The number of patients progressing to rescue oral corticosteroids during a clinical deterioration whilst on benralizumab. | up to 56 or 80 weeks |
| Blood eosinophil counts during a clinical deterioration whilst on benralizumab | up to 56 or 80 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of the magnitude of response to benralizumab - change in lung function, as measured by FEV1, at 16, 24 and 56 weeks compared to baseline | 16, 24 and 56 weeks | FEV1 post salbutamol on spirometry and FEV1 in daily diary |
| Measurement of the magnitude of response to benralizumab - change in lung function at 16, 24 and 56 weeks compared to baseline | 16, 24 and 56 weeks | peak expiratory flow from the daily electronic meter |
| Measurement of the magnitude of response to benralizumab - change in patient reported outcomes at 16,24 and 56 weeks compared to baseline | 16, 24 and 56 weeks | Completion of health outcome questionnaires |
| Identifying predictors of treatment response | 16 weeks and 1 year | Patients will be classified into treatment responders and non-responders. Logistic regression will be used to identify the predictive value of improvement in early clinical response indicators at 16 weeks on 12 month treatment response. |
| Comparing patient reported outcome measures | 16, 24 and 56 weeks | Correlation of completed questionnaires: Scores, and changes in scores, from the SAQ will be correlated with the SGRQ and mini-AQLQ. The SAQ score will be evaluated against demographic features at baseline. |
| Exploratory Microbiomics | baseline, 4, 16 and 56 weeks, during exacerbation visits | Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response |
| Exploratory viromics | baseline, 4, 16 and 56 weeks, during exacerbation visits | Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response |
| Exploratory transcriptomics | baseline, 4, 16 and 56 weeks, during exacerbation visits | Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response |
| Exploratory biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways | baseline, 4, 16 and 56 weeks, during exacerbation visits | Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response |
| Onset of clinical response | up to 56 or 80 weeks | Time to first exacerbation and change in FEV1 with time. |
| Measurement of the magnitude of response to benralizumab - oral steroid reduction with benralizumab at 56 weeks | 56 weeks | proportion of patients who reduce high dose steroid courses and/or maintenance steroid dose by \>=25%, 50%, 75% and 100% |
| Measurement of the magnitude of response to benralizumab - numbers of participants with and early and final good response | 16, 24 weeks, 1 year | Early (16/24 weeks): A GETE response of 'good' or 'excellent' to treatment with benralizumab as determined by the study physician. Final (one year): defined as a reduction of high dose corticosteroid courses by \>=50% compared to the previous year and/or reduction of maintenance oral steroid dose by \>=50% |
| Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline | 16, 56 weeks | FBC to include Blood eosinophils, sputum eosinophils, blood neutrophil counts |
Other
| Measure | Time frame | Description |
|---|---|---|
| Validation of home spirometry with video supported tests | Baseline, 2 and 24 weeks | Comparison of spirometry done on site with another done off site with video support from the study team. |
Countries
United Kingdom
Outcome results
None listed