AsthmaPhase 4NCT04585997
Comparing Treatment Efficacy With Mepolizumab and Omalizumab in Severe Asthma - "Choosebetweenamab".
A Phase 4 study testing Mepolizumab and Omalizumab in people with Asthma and Eosinophilic Asthma, run by University of Newcastle, Australia at 1 site in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 85 years
- Conditions the study is for
- Asthma, Eosinophilic Asthma
- What is being tested?
- Mepolizumab and Omalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteAustralia
- Study dates
- 3 Nov 2018to Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Do not fulfil inclusion criteria
- Unable to attend appointments
- Significant psychiatric illness
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
John Hunter Hospital
New Lambton, New South Wales, 2305
Peter Wark, MBBS/PhD, (02) 40420110, peter.wark@health.nsw.gov.au
Gerard Kaiko, PhD, (02) 40420184, gerard.kaiko@newcastle.edu.au
About this study
Official title: How to "Choosebetweenamab" for Severe Asthma, Comparing Treatment With Mepolizumab and Omalizumab for Patients With Severe Allergic and Eosinophilic Asthma.
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.
Read the 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.
- Conditions
- Asthma, Eosinophilic Asthma
- Being tested
- Mepolizumab, Omalizumab
- Medical subject headings
- Asthma, Pulmonary Eosinophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabDrug
Also called Nucala
Mepolizumab 100mg subcutaneous injection monthly for 6 months
OmalizumabDrug
Also called Xolair
Omalizumab subcutaneous injection every 2-4 weeks (dosage determined by the Omalizumab nomogram).
| Study group | Role | What they receive |
|---|---|---|
| Mepolizumab | Active comparator | Mepolizumab Receives: Drug: Mepolizumab |
| Omalizumab | Active comparator | Omalizumab Receives: Drug: Omalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
ACQ5
The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5
Measured: Assessed after 6 months treatment
Secondary outcomes (10)
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
Measured: every month up to 6 months after treatment commenced
Time to first exacerbation reported, by patient or health provider
Time to first exacerbation reported, by patient or health provider
Measured: every month up to 6 months after treatment commenced
Hospital admissions
Number of admissions to hospital patient reported
Measured: 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
Measured: every month up to 6 months after treatment commenced
Spirometry
Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment
Measured: 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
Measured: 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
Measured: every month up to 6 months after treatment commenced
Emergency department presentation
Number of emergency department presentations, patient and health care provider reported
Measured: 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
Measured: 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: Measured prior to treatment and clinical outcomes at 6 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start3 Nov 2018
- Primary completionJun 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Newcastle, Australia
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Professor Peter Wark, University of Newcastle, Australia
- Investigators
- Peter Wark, MBBS/PhD, Principal investigator, University of Newcastle and Hunter New England Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04585997
- Sponsor's protocol ID
- 18/08/15/3.01
- Status last verified
- Oct 2020
- First submitted
- 30 Sep 2020
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- How to "Choosebetweenamab" for Severe Asthma, Comparing Treatment With Mepolizumab and Omalizumab for Patients With Severe Allergic and Eosinophilic Asthma.
- ClinicalTrials.gov ID
- NCT04585997
- Acronym / sponsor ID
- 18/08/15/3.01
- Conditions
- Asthma, Eosinophilic Asthma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of Newcastle, AustraliaUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 3 Nov 2018 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 14 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mepolizumab | Active comparator | Drug: MepolizumabMepolizumab |
| Omalizumab | Active comparator | Drug: OmalizumabOmalizumab |
Who may qualify
- Ages
- 12 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- Do not fulfil inclusion criteria
- Unable to attend appointments
- Significant psychiatric illness
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MepolizumabAlso: NucalaMepolizumab 100mg subcutaneous injection monthly for 6 months | Drug | Mepolizumab |
| OmalizumabAlso: XolairOmalizumab subcutaneous injection every 2-4 weeks (dosage determined by the Omalizumab nomogram). | Drug | Omalizumab |
Primary outcome
ACQ5
Time frame: Assessed after 6 months treatment
The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5
10 secondary outcomes
Exacerbations
Time frame: every month up to 6 months after treatment commenced
Time to first exacerbation reported, by patient or health provider
Time frame: every month up to 6 months after treatment commenced
Hospital admissions
Time frame: every month up to 6 months after treatment commenced
Oral corticosteroids
Time frame: every month up to 6 months after treatment commenced
Spirometry
Time frame: every month up to 6 months after treatment commenced
Continuing treatment
Time frame: 6 months post intervention
Adverse events
Time frame: every month up to 6 months after treatment commenced
Emergency department presentation
Time frame: every month up to 6 months after treatment commenced
Overall dose of oral corticosteroids
Time frame: 6 months post intervention
Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066)
Time frame: Measured prior to treatment and clinical outcomes at 6 months after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Wark, MBBS/PhD principal investigator
University of Newcastle and Hunter New England Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mepolizumab and Omalizumab in people with Asthma and Eosinophilic Asthma, run by University of Newcastle, Australia at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter Wark, MBBS/PhD ((02) 40420110, peter.wark@health.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACQ5 (time frame: Assessed after 6 months treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2020.