Comparing Treatment Efficacy With Mepolizumab and Omalizumab in Severe Asthma - "Choosebetweenamab".
Comparing Treatment Efficacy With Mepolizumab and Omalizumab in Severe Asthma - "Choosebetweenamab".
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.
'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.
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