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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04585997




Registration number
NCT04585997
Ethics application status
Date submitted
30/09/2020
Date registered
14/10/2020
Date last updated
14/10/2020

Titles & IDs
Public title
Comparing Treatment Efficacy With Mepolizumab and Omalizumab in Severe Asthma - "Choosebetweenamab".
Scientific title
How to "Choosebetweenamab" for Severe Asthma, Comparing Treatment With Mepolizumab and Omalizumab for Patients With Severe Allergic and Eosinophilic Asthma.
Secondary ID [1] 0 0
18/08/15/3.01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Eosinophilic Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mepolizumab
Treatment: Drugs - Omalizumab

Active Comparator: Mepolizumab - Mepolizumab

Active Comparator: Omalizumab - Omalizumab


Treatment: Drugs: Mepolizumab
Mepolizumab 100mg subcutaneous injection monthly for 6 months

Treatment: Drugs: Omalizumab
Omalizumab subcutaneous injection every 2-4 weeks (dosage determined by the Omalizumab nomogram).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ACQ5 - The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5
Timepoint [1] 0 0
Assessed after 6 months treatment
Secondary outcome [1] 0 0
Exacerbations - Number of Exacerbations, requiring change in oral corticosteroids, with either a course of prednisone for at least 3 days, or in those on regular OCS an increase in dose of at least 50% for at least 3 days. Patient reported monthly
Timepoint [1] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [2] 0 0
Time to first exacerbation reported, by patient or health provider - Time to first exacerbation reported, by patient or health provider
Timepoint [2] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [3] 0 0
Hospital admissions - Number of admissions to hospital patient reported
Timepoint [3] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [4] 0 0
Oral corticosteroids - Reduction in dose of regular OCS, confirmed by health care provider and patient reported
Timepoint [4] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [5] 0 0
Spirometry - Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment
Timepoint [5] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [6] 0 0
Continuing treatment - Proportion continuing on Australian PBS treatment (successful treatment). The number at the conclusion of the 6 months that will continue treatment. reported by health provider
Timepoint [6] 0 0
6 months post intervention
Secondary outcome [7] 0 0
Adverse events - Adverse events; i.e. injection site reaction, reported. Headaches, reported, rash, reported, allergic reaction, reported. Any other relevant adverse event report. Patient and health care provider reported
Timepoint [7] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [8] 0 0
Emergency department presentation - Number of emergency department presentations, patient and health care provider reported
Timepoint [8] 0 0
every month up to 6 months after treatment commenced
Secondary outcome [9] 0 0
Overall dose of oral corticosteroids - Overall dose of systemic corticosteroids used during the 6 months after treatment commences. Patients and health care provided
Timepoint [9] 0 0
6 months post intervention
Secondary outcome [10] 0 0
Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066) - ISS 11066 is a substudy of Choosebetweenamab using transcriptomic single cell sequencing of patient white blood cells from both treatment groups at baseline. The data generated from this will be compared to the above clinical outcomes at all follow-up time points. Single cell gene expression and cell type cluster patterning delineated through bioinformatic data processing will be inputted with clinical outcomes into a GLM to identify baseline predictors (gene and cell type) of treatment effect
Timepoint [10] 0 0
Measured prior to treatment and clinical outcomes at 6 months after treatment

Eligibility
Key inclusion criteria
- Participants must have a duration of asthma of greater than one year.

- They must have confirmed asthma defined as: (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 hyperresponsiveness 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.

- They must have evidence of poor asthma control despite optimal ICS and long acting
beta agonist (LABA), be treated by a respiratory physician or immunologist, and have
demonstrated acceptable adherence and inhaler technique. Poor control is defined as:
evidence of an FEV1 <80% of predicted in the last year on at least one occasion;
treatment with OCS, either daily for at least 6 weeks, or a cumulative dose of OCS of
at least 500 mg prednisolone equivalent in the previous 12 months, unless
contraindicated or not tolerated.

- In addition they must demonstrate an: (a) an Asthma Control Questionnaire (ACQ-5)38
score of at least 2.0, as assessed in the previous month, and (b) while receiving
optimised asthma therapy in the past 12 months, experienced at least 1 admission to
hospital for a severe asthma exacerbation, or 1 severe asthma exacerbation, requiring
documented use of OCS initiated or increased for at least 3 days, or parenteral
corticosteroids prescribed/supervised by a physician.

- They must also demonstrate evidence of a dual allergic/ eosinophilic phenotype. This
is defined as: a total serum IgE >30IU/mL, past or current evidence of atopy
documented by skin prick testing or radioallergosorbent assay, and the participant
must have a blood eosinophil count greater than or equal to 300 cells per microlitre
in the last 6 weeks.
Minimum age
12 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Do not fulfil inclusion criteria

- Unable to attend appointments

- Significant psychiatric illness

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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] 0 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 0 0
2305 - New Lambton

Funding & Sponsors
Primary sponsor type
Other
Name
University of Newcastle, Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Mepolizumab is an anti-interleukin-5 ( IL-5) monoclonal antibody that neutralizes IL-5 and
reduces eosinophil counts in both sputum and blood. Omalizumab is an anti-immunoglobulin E
(IgE) monoclonal antibody (mAb) used in the treatment of severe allergic eosinophilic asthma

The investigators propose that in patients with the dual phenotypes of severe allergic and
eosinophilic asthma, that Mepolizumab is as effective as Omalizumab. However, this trial will
also identify key clinical biomarkers that will clarify which patients will respond best to
each of these interventions.

This study will be the first direct clinical comparison of these agents and will apply expert
clinical characterization, along with cutting edge biotechnology to better inform treatment
choices for severe asthma. This is an important and urgent management problem facing the
Australian pharmaceutical scheme, where imprecision in prescribing will result in reduced
clinical effectiveness as well as substantial and sustained costs.
Trial website
https://clinicaltrials.gov/show/NCT04585997
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Wark, MBBS/PhD
Address 0 0
University of Newcastle and Hunter New England Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Peter Wark, MBBS/PhD
Address 0 0
Country 0 0
Phone 0 0
(02) 40420110
Fax 0 0
Email 0 0
peter.wark@health.nsw.gov.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04585997