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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mepolizumab | Active Comparator | Mepolizumab |
|
| Omalizumab | Active Comparator | Omalizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mepolizumab | Drug | Mepolizumab 100mg subcutaneous injection monthly for 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| ACQ5 | The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5 | Assessed after 6 months treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Exacerbations | 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 | every month up to 6 months after treatment commenced |
| Time to first exacerbation reported, by patient or health provider |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Peter Wark, MBBS/PhD | Contact | (02) 40420110 | peter.wark@health.nsw.gov.au | |
| Gerard Kaiko, PhD | Contact | (02) 40420184 | gerard.kaiko@newcastle.edu.au |
| Name | Affiliation | Role |
|---|---|---|
| Peter Wark, MBBS/PhD | University of Newcastle and Hunter New England Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| John Hunter Hospital | Recruiting | New Lambton | New South Wales | 2305 | Australia |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jul 17, 2019 | Sep 30, 2020 | ICF_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jun 19, 2020 | Sep 30, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| D011657 | Pulmonary Eosinophilia |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C434107 | mepolizumab |
| D000069444 | Omalizumab |
| ID | Term |
|---|---|
| D000888 | Antibodies, Anti-Idiotypic |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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People assessing outcomes and analyzing results are blinded
| Omalizumab | Drug | Omalizumab subcutaneous injection every 2-4 weeks (dosage determined by the Omalizumab nomogram). |
|
|
Time to first exacerbation reported, by patient or health provider |
| every month up to 6 months after treatment commenced |
| Hospital admissions | Number of admissions to hospital patient reported | every month up to 6 months after treatment commenced |
| Oral corticosteroids | Reduction in dose of regular OCS, confirmed by health care provider and patient reported | every month up to 6 months after treatment commenced |
| Spirometry | Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment | every month up to 6 months after treatment commenced |
| Continuing treatment | 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 | 6 months post intervention |
| Adverse events | 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 | every month up to 6 months after treatment commenced |
| Emergency department presentation | Number of emergency department presentations, patient and health care provider reported | every month up to 6 months after treatment commenced |
| Overall dose of oral corticosteroids | Overall dose of systemic corticosteroids used during the 6 months after treatment commences. Patients and health care provided | 6 months post intervention |
| Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066) | 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 | Measured prior to treatment and clinical outcomes at 6 months after treatment |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D017681 | Hypereosinophilic Syndrome |
| D004802 | Eosinophilia |
| D007960 | Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D012712 | Serum Globulins |
| D005916 | Globulins |