ANZCTR - Registration

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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

14/11/2024

Date data sharing statement initially provided

30/11/2018

Date results provided

14/11/2024

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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

severe asthma

Condition category

Condition code

Respiratory

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]

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]

The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5.

Timepoint [1]

Assessed after 6 months treatment

Secondary outcome [1]

• 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]

every month up to 6 months after treatment commenced

Secondary outcome [2]

• Time to first exacerbation reported, by patient or health provider

Timepoint [2]

every month up to 6 months after treatment commenced

Secondary outcome [3]

• Number of admissions to hospital patient reported

Timepoint [3]

every month up to 6 months after treatment commenced

Secondary outcome [4]

• Reduction in dose of regular OCS, confirmed by health care provider and patient reported

Timepoint [4]

every month up to 6 months after treatment commenced

Secondary outcome [5]

• Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment.

Timepoint [5]

every month up to 6 months after treatment commenced

Secondary outcome [6]

• Change in blood eosinophils

Timepoint [6]

every month up to 6 months after treatment commenced

Secondary outcome [7]

• 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]

6 months post intervention

Secondary outcome [8]

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]

every month up to 6 months after treatment commenced

Secondary outcome [9]

Number of emergency department presentations, patient and health care provider reported

Timepoint [9]

every month up to 6 months after treatment commenced

Secondary outcome [10]

overal dose of systemic corticosteroids used during the 6 months after treatment commences. Patients and health care provided.

Timepoint [10]

at 6 months post intervention.

Secondary outcome [11]

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]

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?

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. Sample size calculations indicated that 92 participants was sufficient for analysis of the trial outcomes using a non-inferiority analysis approach for the primary outcomes between the two parallel treatment arms.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

10/09/2018

Actual

3/11/2018

Date of last participant enrolment

Anticipated

3/05/2021

Actual

7/03/2023

Date of last data collection

Anticipated

6/06/2022

Actual

31/08/2023

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

John Hunter Hospital - New Lambton

Recruitment postcode(s) [1]

2305 - New Lambton

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Glaxo Smith Kline

Address [1]

GSK Pharmaceuticals and Vaccines
Level 3, 436 Johnston Street, Abbotsford, Victoria, 3067

PO Box 18095, Melbourne, Victoria, 8003

Country [1]

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]

Commercial sector/Industry

Name [1]

GSK

Address [1]

GSK Pharmaceuticals and Vaccines
Level 3, 436 Johnston Street, Abbotsford, Victoria, 3067

PO Box 18095, Melbourne, Victoria, 8003

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England LHD Ethics committee

Ethics committee address [1]

Lookout Rd New Lambton NSW 2305

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

08/06/2018

Approval date [1]

14/09/2018

Ethics approval number [1]

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

Prof Peter Wark

Address

Centre for Healthy Lungs HMRI
Lookout Rd New Lambton NSW 2305

Country

Australia

Phone

+61, 2, 49213309

Fax

+61 24921369

peter.wark@hnehealth.nsw.gov.au

Contact person for public queries

Name

Peter Wark

Address

Centre for Healthy Lungs HMRI
Lookout Rd New Lambton NSW 2305

Country

Australia

Phone

+61 2 49213309

Fax

+61, 2, 40420046

peter.wark@hnehealth.nsw.gov.au

Contact person for scientific queries

Name

Peter Wark

Address

Centre for Healthy Lungs HMRI
Lookout Rd New Lambton NSW 2305

Country

Australia

Phone

+61, 2, 49213309

Fax

61, 2, 4921369

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.	Type	Email	Other Details	Attachment
566	Study protocol			374673-(Uploaded-29-11-2018-13-23-33)-Study-related document.docx
567	Informed consent form			374673-(Uploaded-29-11-2018-13-24-18)-Study-related document.doc
568	Ethical approval			374673-(Uploaded-29-11-2018-13-25-05)-Study-related document.pdf
9762	Study protocol	gerard.kaiko@newcastle.edu.au		374673-(Uploaded-12-08-2020-20-54-58)-Study-related document.pdf
9763	Statistical analysis plan		Provided in study protocol document
9764	Clinical study report		Provided at the conclusion of the trial.

Results publications and other study-related documents

Documents added manually

Current Study Results

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Conference abstract	Yes			CBMaB ERS abstract final.docx
Supplementary materials	No			Results of sub-study ISS 11066 .docx

Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
5064	Conference abstract	Yes			CBMaB ERS abstract final.docx
5089	Supplementary materials	No			Results of sub-study ISS 11066 .pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.	2021	https://dx.doi.org/10.1111/imj.14806

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically