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Trial registered on ANZCTR


Registration number
ACTRN12618000850279
Ethics application status
Approved
Date submitted
7/03/2018
Date registered
21/05/2018
Date last updated
16/11/2020
Date data sharing statement initially provided
30/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
How to "choosebetweenamab" for severe asthma, comparing treatment with mepolizumab and omalizumab for patients with severe allergic and eosinophilic asthma.
Scientific title
How to "choosebetweenamab" for severe asthma, Mepolizumab is as effective as Omalizumab in improving asthma symptom control, as measured by the asthma control questionnaire (ACQ5), for patients with severe allergic and eosinophilic asthma.
Secondary ID [1] 294920 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
severe asthma 306947 0
Condition category
Condition code
Respiratory 306046 306046 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment will be either mepolizumab 100mg subcutaneous injection monthly for 6 months or Omalizumab subcutaneous injection every 2-4 weeks (dosage determined by the Omalizumab nomogram). Administered by a nurse.
Intervention code [1] 300556 0
Treatment: Drugs
Comparator / control treatment
Subjects will receive either Mepolizumab or Omalizumab. There is no placebo control.
Mepolizumab/Omalizumab
Control group
Active

Outcomes
Primary outcome [1] 305073 0
The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5.
Timepoint [1] 305073 0
Assessed after 6 months treatment
Secondary outcome [1] 344091 0
• 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] 344091 0
every month up to 6 months after treatment commenced
Secondary outcome [2] 344092 0
• Time to first exacerbation reported, by patient or health provider
Timepoint [2] 344092 0
every month up to 6 months after treatment commenced
Secondary outcome [3] 344093 0
• Number of admissions to hospital patient reported
Timepoint [3] 344093 0
every month up to 6 months after treatment commenced
Secondary outcome [4] 344094 0
• Reduction in dose of regular OCS, confirmed by health care provider and patient reported
Timepoint [4] 344094 0
every month up to 6 months after treatment commenced
Secondary outcome [5] 344095 0
• Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment.
Timepoint [5] 344095 0
every month up to 6 months after treatment commenced
Secondary outcome [6] 344096 0
• Change in blood eosinophils
Timepoint [6] 344096 0
every month up to 6 months after treatment commenced
Secondary outcome [7] 344097 0
• 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 [7] 344097 0
6 months post intervention
Secondary outcome [8] 344098 0
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 [8] 344098 0
every month up to 6 months after treatment commenced
Secondary outcome [9] 346952 0
Number of emergency department presentations, patient and health care provider reported
Timepoint [9] 346952 0
every month up to 6 months after treatment commenced
Secondary outcome [10] 346955 0
overal dose of systemic corticosteroids used during the 6 months after treatment commences. Patients and health care provided.
Timepoint [10] 346955 0
at 6 months post intervention.
Secondary outcome [11] 388947 0
Change in immune response as measured by single cell sequencing of peripheral blood cells.
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 [11] 388947 0
Measured prior to treatment and 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Do not fulfil inclusion criteria
Unable to attend appointments
Significant psychiatric illness
Unable to speak English

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)
Central computer generated randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
permuted block randomisation, with block sizes of 4 or 6, stratified by baseline eosinophil count (using a median split).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Efficacy of the intervention: All analyses will be conducted blind to group allocation. The primary endpoint will be analysed for the as treated population to minimise type I error inflation by treatment failure and subsequent crossover. A sensitivity analysis will be performed for the intention-to-treat (ITT) population.
Treatment group differences in six-month ACQ5 will be estimated using a Generalised Linear Model (GLM) with a normal response distribution and identity link function. The model will be fitted in an ANCOVA framework (i.e., adjusted for baseline). The model will include fixed effects for group and baseline eosinophil count. The treatment effects will be estimated as baseline-adjusted, least-square mean differences between the two treatment groups at 6 month follow-up. Secondary analyses will be assessed using the same GLM approach, with response link function as appropriate to the response distribution.
Attrition: The GLM provides unbiased estimates of treatment effect under the assumption that data are missing completely at random. Based on previous experience with this patient population, attrition is anticipated to be very low. However, sensitivity analyses such as multiple imputation and pattern mixture modelling will be used to investigate the robustness of conclusions to different missing data mechanisms.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/09/2018
Actual
3/11/2018
Date of last participant enrolment
Anticipated
3/05/2021
Actual
Date of last data collection
Anticipated
6/06/2022
Actual
Sample size
Target
200
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 10320 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 21988 0
2305 - New Lambton
Recruitment outside Australia
Country [1] 9659 0
New Zealand
State/province [1] 9659 0

Funding & Sponsors
Funding source category [1] 298903 0
Commercial sector/Industry
Name [1] 298903 0
Glaxo Smith Kline
Country [1] 298903 0
Australia
Primary sponsor type
Individual
Name
Peter Wark
Address
Centre for Healthy Lungs, HMRI, University of Newcastle. Lookout Rd New Lambton NSW 2305
Country
Australia
Secondary sponsor category [1] 298118 0
Commercial sector/Industry
Name [1] 298118 0
GSK
Address [1] 298118 0
GSK Pharmaceuticals and Vaccines
Level 3, 436 Johnston Street, Abbotsford, Victoria, 3067

PO Box 18095, Melbourne, Victoria, 8003
Country [1] 298118 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299845 0
Hunter New England LHD Ethics committee
Ethics committee address [1] 299845 0
Lookout Rd New Lambton NSW 2305
Ethics committee country [1] 299845 0
Australia
Date submitted for ethics approval [1] 299845 0
08/06/2018
Approval date [1] 299845 0
14/09/2018
Ethics approval number [1] 299845 0
HNEHREC Reference No: 18/08/15/3.01

Summary
Brief summary
Hypothesis: We propose in patients with the dual phenotypes of severe allergic and eosinophilic asthma, that Mepolizumab is as effective as Omalizumab. However, we will also go on and 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
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81750 0
Prof Peter Wark
Address 81750 0
Centre for Healthy Lungs HMRI
Lookout Rd New Lambton NSW 2305
Country 81750 0
Australia
Phone 81750 0
+61, 2, 49213309
Fax 81750 0
+61 24921369
Email 81750 0
peter.wark@hnehealth.nsw.gov.au
Contact person for public queries
Name 81751 0
Prof Peter Wark
Address 81751 0
Centre for Healthy Lungs HMRI
Lookout Rd New Lambton NSW 2305
Country 81751 0
Australia
Phone 81751 0
+61 2 49213309
Fax 81751 0
+61, 2, 40420046
Email 81751 0
peter.wark@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 81752 0
Prof Peter Wark
Address 81752 0
Centre for Healthy Lungs HMRI
Lookout Rd New Lambton NSW 2305
Country 81752 0
Australia
Phone 81752 0
+61, 2, 49213309
Fax 81752 0
61, 2, 4921369
Email 81752 0
peter.wark@hnehealth.nsw.gov.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
When will data be available (start and end dates)?
At the conclusion of the trial
Available to whom?
Researchers
Available for what types of analyses?
Any
How or where can data be obtained?
Written request for data approved by the PIs


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
566Study protocol    374673-(Uploaded-29-11-2018-13-23-33)-Study-related document.docx
567Informed consent form    374673-(Uploaded-29-11-2018-13-24-18)-Study-related document.doc
568Ethical approval    374673-(Uploaded-29-11-2018-13-25-05)-Study-related document.pdf
9762Study protocol  gerard.kaiko@newcastle.edu.au 374673-(Uploaded-12-08-2020-20-54-58)-Study-related document.pdf
9763Statistical analysis plan    Provided in study protocol document
9764Clinical study report    Provided at the conclusion of the trial.



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSevere asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.2021https://dx.doi.org/10.1111/imj.14806
N.B. These documents automatically identified may not have been verified by the study sponsor.