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

How to "Choosebetweenamab" for Severe Asthma, Comparing Treatment With Mepolizumab and Omalizumab for Patients With Severe Allergic and Eosinophilic Asthma.

Sponsors

Lead Sponsor: University of Newcastle, Australia

Collaborator: GlaxoSmithKline

Source University of Newcastle, Australia
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.

Overall Status Recruiting
Start Date November 3, 2018
Completion Date December 2022
Primary Completion Date June 2022
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
ACQ5 Assessed after 6 months treatment
Secondary Outcome
Measure Time Frame
Exacerbations every month up to 6 months after treatment commenced
Time to first exacerbation reported, by patient or health provider every month up to 6 months after treatment commenced
Hospital admissions every month up to 6 months after treatment commenced
Oral corticosteroids every month up to 6 months after treatment commenced
Spirometry every month up to 6 months after treatment commenced
Continuing treatment 6 months post intervention
Adverse events every month up to 6 months after treatment commenced
Emergency department presentation every month up to 6 months after treatment commenced
Overall dose of oral corticosteroids 6 months post intervention
Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066) Measured prior to treatment and clinical outcomes at 6 months after treatment
Enrollment 200
Condition
Intervention

Intervention Type: Drug

Intervention Name: Mepolizumab

Description: Mepolizumab 100mg subcutaneous injection monthly for 6 months

Arm Group Label: Mepolizumab

Other Name: Nucala

Intervention Type: Drug

Intervention Name: Omalizumab

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

Arm Group Label: Omalizumab

Other Name: Xolair

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

Gender: All

Minimum Age: 12 Years

Maximum Age: 85 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Peter Wark, MBBS/PhD Principal Investigator University of Newcastle and Hunter New England Health
Overall Contact

Last Name: Peter Wark, MBBS/PhD

Phone: (02) 40420110

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: John Hunter Hospital Peter Wark, MBBS/PhD (02) 40420110 [email protected]
Location Countries

Australia

Verification Date

October 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Newcastle, Australia

Investigator Full Name: Professor Peter Wark

Investigator Title: Professor and Senior Staff Respiratory Specialist

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Mepolizumab

Type: Active Comparator

Description: Mepolizumab

Label: Omalizumab

Type: Active Comparator

Description: Omalizumab

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Single (Outcomes Assessor)

Masking Description: People assessing outcomes and analyzing results are blinded

Source: ClinicalTrials.gov