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

Primary Purpose

Asthma, Eosinophilic Asthma

Status

Unknown status

Phase

Phase 4

Locations

Australia

Study Type

Interventional

Intervention

Mepolizumab

Omalizumab

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

12 Years - 85 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

John Hunter HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Mepolizumab

Omalizumab

Arm Description

Mepolizumab

Omalizumab

Outcomes

Primary Outcome Measures

ACQ5

The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5

Secondary Outcome Measures

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

Time to first exacerbation reported, by patient or health provider

Hospital admissions

Number of admissions to hospital patient reported

Oral corticosteroids

Reduction in dose of regular OCS, confirmed by health care provider and patient reported

Spirometry

Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment

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

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

Emergency department presentation

Number of emergency department presentations, patient and health care provider reported

Overall dose of oral corticosteroids

Overall dose of systemic corticosteroids used during the 6 months after treatment commences. Patients and health care provided

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

Full Information

NCT ID

NCT04585997

First Posted

September 30, 2020

Last Updated

October 6, 2020

Sponsor

University of Newcastle, Australia

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT04585997

Brief Title

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Unknown status

Study Start Date

November 3, 2018 (Actual)

Primary Completion Date

June 2022 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Newcastle, Australia

Collaborators

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma, Eosinophilic Asthma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Masking Description

People assessing outcomes and analyzing results are blinded

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mepolizumab

Arm Type

Active Comparator

Arm Description

Mepolizumab

Arm Title

Omalizumab

Arm Type

Active Comparator

Arm Description

Omalizumab

Intervention Type

Drug

Intervention Name(s)

Mepolizumab

Other Intervention Name(s)

Nucala

Intervention Description

Mepolizumab 100mg subcutaneous injection monthly for 6 months

Intervention Type

Drug

Intervention Name(s)

Omalizumab

Other Intervention Name(s)

Xolair

Intervention Description

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

Primary Outcome Measure Information:

Title

ACQ5

Description

The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5

Time Frame

Assessed after 6 months treatment

Secondary Outcome Measure Information:

Title

Exacerbations

Description

Time Frame

every month up to 6 months after treatment commenced

Title

Time to first exacerbation reported, by patient or health provider

Description

Time to first exacerbation reported, by patient or health provider

Time Frame

every month up to 6 months after treatment commenced

Title

Hospital admissions

Description

Number of admissions to hospital patient reported

Time Frame

every month up to 6 months after treatment commenced

Title

Oral corticosteroids

Description

Reduction in dose of regular OCS, confirmed by health care provider and patient reported

Time Frame

every month up to 6 months after treatment commenced

Title

Spirometry

Description

Change in spirometry, FEV1., measured at time treatment commences and 6 months after treatment

Time Frame

every month up to 6 months after treatment commenced

Title

Continuing treatment

Description

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

Time Frame

6 months post intervention

Title

Adverse events

Description

Time Frame

every month up to 6 months after treatment commenced

Title

Emergency department presentation

Description

Number of emergency department presentations, patient and health care provider reported

Time Frame

every month up to 6 months after treatment commenced

Title

Overall dose of oral corticosteroids

Description

Overall dose of systemic corticosteroids used during the 6 months after treatment commences. Patients and health care provided

Time Frame

6 months post intervention

Title

Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066)

Description

Time Frame

Measured prior to treatment and clinical outcomes at 6 months after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Peter Wark, MBBS/PhD

Phone

(02) 40420110

peter.wark@health.nsw.gov.au

First Name & Middle Initial & Last Name or Official Title & Degree

Gerard Kaiko, PhD

Phone

(02) 40420184

gerard.kaiko@newcastle.edu.au

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peter Wark, MBBS/PhD

Organizational Affiliation

University of Newcastle and Hunter New England Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

John Hunter Hospital

City

New Lambton

State/Province

New South Wales

ZIP/Postal Code

2305

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Peter Wark, MBBS/PhD

Phone

(02) 40420110

peter.wark@health.nsw.gov.au

First Name & Middle Initial & Last Name & Degree

Gerard Kaiko, PhD

Phone

(02) 40420184

gerard.kaiko@newcastle.edu.au

12. IPD Sharing Statement

Learn more about this trial

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

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