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Trial registered on ANZCTR


Registration number
ACTRN12621000113853p
Ethics application status
Submitted, not yet approved
Date submitted
23/11/2020
Date registered
4/02/2021
Date last updated
4/02/2021
Date data sharing statement initially provided
4/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of mepolizumab on alternative functions of eosinophils in severe eosinophilic asthma
Scientific title
A single-site cross-sectional cohort study with longitudinal follow-up to investigate the effect of mepolizumab treatment on homeostatic and induced eosinophils, eosinophil extracellular traps, mast cells and basophils in people with severe eosinophilic asthma
Secondary ID [1] 302749 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ALTEOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe asthma 319693 0
Condition category
Condition code
Respiratory 317620 317620 0 0
Asthma
Inflammatory and Immune System 317621 317621 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A cross-sectional observational study will be conducted in participants with stable severe asthma.

Participants will be categorized into three groups:
1. Stable severe asthma not treated with biologics without elevated blood eosinophils (non-eosinophilic)
2. Stable severe asthma not treated with biologics with elevated blood eosinophils (eosinophilic)
3. Stable severe asthma currently receiving mepolizumab treatment

All participants in groups 1,2 and 3 will attend a cross-sectional study visit. Participants in group 2 who commence mepolizumab (Nucala) or benralizumab (Fasenra) treatment as part of their routine clinical care subsequent to the initial cross-sectional study visit will also attend longitudinal follow up study visits at >4 weeks post treatment commencement and >6 months post treatment commencement.

Each study visit (cross-sectional and longitudinal) will involve collection of blood and induced sputum samples, spirometry (lung function) tests, measurement of height and weight. The participant will also complete some questionnaires to gain information about general health or quality of life, medical history and medications and asthma symptoms. Study visits are anticipated to be 1-2 hours in duration.

All participants will consent to:
A. Completing the tests involved in the study
B. Completing questionnaires to obtain research data
C. Allowing research personnel to access their medical record

Participants may optionally consent to:
D. Storage of biospecimens for use in future research studies relating to asthma and respiratory disease.
Intervention code [1] 319034 0
Not applicable
Comparator / control treatment
For cross-sectional analyses, comparisons will be made between participant groups 1, 2 and 3:

1. Stable severe asthma not treated with biologics without elevated blood eosinophils (non-eosinophilic)
2. Stable severe asthma not treated with biologics with elevated blood eosinophils (eosinophilic)
3. Stable severe asthma currently receiving mepolizumab treatment

For longitudinal analyses of participants in group 2 who commence mepolizumab or benralizumab as part of their routine clinical care after the cross sectional visit, measures made pre- and post- commencement of these treatments will be compared.
Control group
Active

Outcomes
Primary outcome [1] 325663 0
Comparison of blood eosinophil subpopulation number between severe non-eosinophilic asthma, severe eosinophilic asthma, severe eosinophilic asthma.
Timepoint [1] 325663 0
Cross-sectional (baseline/initial visit for all participants)
Primary outcome [2] 326172 0
Comparison of blood eosinophil subpopulation proportion between severe non-eosinophilic asthma, severe eosinophilic asthma, severe eosinophilic asthma.
Timepoint [2] 326172 0
Cross-sectional (baseline/initial visit for all participants)
Secondary outcome [1] 388724 0
Blood and sputum eosinophil subpopulations.
Timepoint [1] 388724 0
Cross-sectional (baseline/initial visit for all participants)
Secondary outcome [2] 390361 0
Extracellular trap formation in sputum slides and supernatant
Timepoint [2] 390361 0
Cross-sectional (baseline/initial visit for all participants)
Secondary outcome [3] 390362 0
Sputum and blood mast cell and basophil measures.
Timepoint [3] 390362 0
Cross-sectional (baseline/initial visit for all participants)
Secondary outcome [4] 390363 0
Blood and sputum eosinophil subpopulations.
Timepoint [4] 390363 0
Longitudinal (participants in group 2 at baseline/initial visit and at >4 weeks and >6 months post commencement of treatment)
Secondary outcome [5] 390364 0
Extracellular trap formation in sputum slides and supernatant
Timepoint [5] 390364 0
Longitudinal (participants in group 2 at baseline/initial visit and at >4 weeks and >6 months post commencement of treatment)
Secondary outcome [6] 390365 0
Sputum and blood mast cell and basophil measures.
Timepoint [6] 390365 0
Longitudinal (participants in group 2 at baseline/initial visit and at >4 weeks and >6 months post commencement of treatment)

Eligibility
Key inclusion criteria
- Able to provide written informed consent
- Adults aged 18 or over
- Confirmed diagnosis of asthma
- Evidence or documented evidence of asthma defined by variable airflow limitation:
i. Forced expiratory volume (FEV1) reversibility greater than or equal to 12%, and greater than or equal to 200 mL at baseline within 30 minutes after administration of salbutamol (200 to 400 micrograms), OR
ii. Airway hyper-responsiveness defined as a greater than 20% decline in FEV1 during a direct bronchial provocation test or greater than 15% decline during an indirect bronchial provocation test, OR
iii. Peak expiratory flow (PEF) variability of greater than 15% between the two highest and two lowest peak expiratory flow rates during 14 days.

- Participants must have severe asthma. Severe asthma is defined as asthma requiring high-dose inhaled corticosteroids with a second controller to prevent “uncontrolled” disease or disease that remains “uncontrolled” despite therapy. Criteria for severe asthma are as follows:
a. Asthma is uncontrolled* despite adherence with optimized high dose inhaled corticosteroid-long-acting beta-2 agonist (ICS-LABA)# therapy and treatment of contributory factors, or that worsens when high dose treatment is decreased.
b. *Uncontrolled asthma includes one or both of the following:
i. Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma)
ii. Exacerbations (greater than or equal to 1/year) requiring oral corticosteroids (OCS), or serious exacerbations (greater than or equal to 1/year) requiring hospitalization
c. # For GINA definition of high dose ICS see (https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnancy/breastfeeding
- Participants currently receiving or having received in past 6 months treatment with benralizumab or omalizumab.
- No exacerbation of asthma in prior 4 weeks at screening.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Cross-sectional study:

For cross-sectional analyses, comparisons will be made between participant groups 1, 2 and 3 as outlined above. We will perform ANOVA with pre-planned comparisons. Where appropriate, data will be log transformed prior to analysis. Where data are non-normally distributed, Kruskal-Wallis will be used for 3 group comparison.

Longitudinal study: For endpoints within the longitudinal study analysis will be performed comparing baseline visit with follow up visits.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17983 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 31941 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 307170 0
Commercial sector/Industry
Name [1] 307170 0
Glaxo Smith Kline
Address [1] 307170 0
GlaxoSmithKline Research & Development Limited
980 Great West Road, Brentford, Middlesex, UK, 7W8 9GS
Country [1] 307170 0
United Kingdom
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive
Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 307765 0
None
Name [1] 307765 0
Address [1] 307765 0
Country [1] 307765 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307284 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 307284 0
Locked Bag 1
New Lambton
NSW 2305
Ethics committee country [1] 307284 0
Australia
Date submitted for ethics approval [1] 307284 0
20/11/2020
Approval date [1] 307284 0
Ethics approval number [1] 307284 0

Summary
Brief summary
Inflammation in the lungs and circulation can cause asthma symptoms and can be treated with anti-inflammatory medications. For people with severe asthma, the inflammation and associated asthma symptoms are still problematic despite treatment with high dose puffer medications. Eosinophils are a type of cell in the blood and airways that promote inflammation. Mepolizumab (Nucala) and benralizumab (Fasenra) are treatments that can be prescribed for people with a type of severe asthma who have high eosinophil counts in their blood. Mepolizumab and benralizumab lower the number of blood and airway eosinophils and have been shown to reduce asthma flare-ups by about half. Recent research has described some new biological functions of eosinophils in inflammation. This study will aim to determine if these eosinophil functions and other important inflammation processes are a) changed in severe asthma in people with or without high blood eosinophil counts and b) whether any inflammation remains in people treated with mepolizumab or benralizumab. This new knowledge could help researchers to develop new asthma medications and better use existing medications in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106682 0
Dr Michael Fricker
Address 106682 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 106682 0
Australia
Phone 106682 0
+61 2 4042 0207
Fax 106682 0
+61 2 4042 0046
Email 106682 0
michael.fricker@newcastle.edu.au
Contact person for public queries
Name 106683 0
Dr Michael Fricker
Address 106683 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 106683 0
Australia
Phone 106683 0
+61 2 4042 0207
Fax 106683 0
+61 2 4042 0046
Email 106683 0
michael.fricker@newcastle.edu.au
Contact person for scientific queries
Name 106684 0
Dr Michael Fricker
Address 106684 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 106684 0
Australia
Phone 106684 0
+61 2 4042 0207
Fax 106684 0
+61 2 4042 0046
Email 106684 0
michael.fricker@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymised data underlying published results
When will data be available (start and end dates)?
For up to 5 years after publication
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
Any
How or where can data be obtained?
Written request for data must be approved by the PIs (michael.fricker@newcastle.edu.au)
What supporting documents are/will be available?
No other documents available
Summary results
No Results