Clinical trial NCT04585997: Comparing Treatment Efficacy With Mepolizumab and Omalizumab in Severe Asthma - "Choosebetweenamab".
Official title: How to "Choosebetweenamab" for Severe Asthma, Comparing Treatment With Mepolizumab and Omalizumab for Patients With Severe Allergic and Eosinophilic Asthma.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Asthma
Eosinophilic Asthma
Lead sponsor: University of Newcastle, Australia
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2020-10-14
Enrollment: 200
Sex: ALL
Minimum age (years): 12
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 'Choosebetweenamab' will compare active treatment arms (Mepolizumab and Omalizumab) for efficacy and adverse events in a Phase 4, parallel arm, randomized controlled trail setting with computer generated randomization (permuted block randomization, with block sizes of 4 or 6, stratified by baseline eosinophil count using a median split). There is no placebo control. Particpants will not be blinded but masking will be used for people assessing outcomes and analyzing data.

'Chossebetweenamab' will also include a secondary outcome substudy (ISS 11066) to assess biomarkers of efficacy response to treatment using single cell sequencing of peripheral blood cells. Blood samples are taken from the randomized patients in each treatment arm (Mepolizumab and Omalizumab) at baseline and gene expression changes assessed using transcriptomic single cell sequencing of patient white blood cells. The data generated from this will be compared to the clinical outcomes of 'Choosebetweenamab' at all follow-up time points. Single cell gene expression and cell type cluster patterning will be compared to the primary and secondary outcomes to identify baseline predictors (gene and cell type) of treatment efficacy.

Eligibility criteria: 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.

Exclusion Criteria:

* Do not fulfil inclusion criteria
* Unable to attend appointments
* Significant psychiatric illness

Primary outcomes:
measure: ACQ5
timeFrame: Assessed after 6 months treatment
Secondary outcomes:
measure: Exacerbations
timeFrame: every month up to 6 months after treatment commenced
measure: Time to first exacerbation reported, by patient or health provider
timeFrame: every month up to 6 months after treatment commenced
measure: Hospital admissions
timeFrame: every month up to 6 months after treatment commenced
measure: Oral corticosteroids
timeFrame: every month up to 6 months after treatment commenced
measure: Spirometry
timeFrame: every month up to 6 months after treatment commenced
measure: Continuing treatment
timeFrame: 6 months post intervention
measure: Adverse events
timeFrame: every month up to 6 months after treatment commenced
measure: Emergency department presentation
timeFrame: every month up to 6 months after treatment commenced
measure: Overall dose of oral corticosteroids
timeFrame: 6 months post intervention
measure: Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066)
timeFrame: Measured prior to treatment and clinical outcomes at 6 months after treatment
Other outcomes:
Locations:
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
Study officials:
affiliation: University of Newcastle and Hunter New England Health
name: Peter Wark, MBBS/PhD
role: PRINCIPAL_INVESTIGATOR
References: