AsthmaPhase 4BenRexNCT04102800
Benralizumab Exacerbation Study
A Phase 4 study testing Benralizumab in people with Asthma, run by NHS Greater Glasgow and Clyde at 15 sites in United Kingdom.
Trial summary
This is an exploratory study, the focus of which is to understand the nature of asthma exacerbations that occur despite open label benralizumab therapy in severe eosinophilic asthma. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Asthma
- What is being tested?
- Benralizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 15 sitesUnited Kingdom
- Study dates
- 30 Sep 2019to 23 Apr 2024
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- able and willing to provide written informed consent and to comply with the study protocol, including being able to attend for assessment during a symptomatic deterioration
- severe asthma confirmed after assessment by an asthma specialist, requiring treatment with high dose inhaled corticosteroids (ICS) as per BTS criteria [>1000 fluticasone proportionate equivalent] and >1 additional drug for asthma (e.g. long acting beta 2 antagonist (LABA)/leukotriene receptor antagonist/theophylline/long acting muscarinic antagonist) at screening [participants may be included with a lower dose of current ICS at the discretion of the investigator if previous high ICS dose had led to side effects]
- Adherent with background asthma medication in the opinion of the investigator [adherence assessments as per local practice]
- Assessed and treatment optimised for any significant asthma-related co-morbidities
- Considered suitable by an asthma specialist for treatment with a monoclonal antibody to block the Interleukin-5 pathway as per local practice. Participants will have: a) recorded blood eosinophil count ≥0.3 x 109/L within the past year along with a history of either ≥4 asthma exacerbations requiring high dose oral corticosteroids* and/or maintenance systemic corticosteroids equivalent to prednisolone ≥5 mg/day for 6 months or longer OR b) recorded blood eosinophil count ≥0.4 x 109/L within the past year along with a history of ≥ 3 asthma exacerbations requiring high dose oral corticosteroids*
- [Exacerbations of asthma in the past year will be defined as worsening of asthma symptoms leading to treatment with prednisolone ≥30 mg oral corticosteroids for ≥3 days or an increase ≥ 10mg in oral corticosteroids for at least 3 days for patients on maintenance oral steroids] as defined by the ERS/ATS Task Force
Who cannot join
- Acute exacerbation requiring high dose oral corticosteroids in the 2 weeks prior to Visit 1 or during the screening period. Such patients would be re-assessed after 2 weeks for re-screening.
- Other clinically significant medical disease or uncontrolled concomitant disease that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study.
- History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.
- Female patients who are pregnant or lactating or planning a family
- Active lung disease other than asthma [Note: Controlled obstructive sleep apnoea (OSA), minor bronchiectasis, asbestos pleural plaques or old (inactive) TB scars are not exclusion criteria]. Patients where an asthma-COPD overlap is suspected by the investigator are not eligible for inclusion.
- Current smoker [history of smoking [including e-cigarettes] in the past 3 months prior to Visit 1.
Show all 19Show fewer
- Treatment with any of the following prior to Visit 1 or during the study
- any biologic medicine for asthma or an immunomodulating biologic agent for other conditions in the 3 months prior to Visit 1
- an investigational agent within 30 days of Visit 1 (or five half lives of the investigational agent, whichever is longer).
- Administration of live attenuated vaccine 30 days prior to Visit 1. Other types of approved vaccines are allowed.
- Regular use of systemic (oral/IM) corticosteroids except for the indication of asthma or adrenal insufficiency [note: patients taking systemic steroid replacement primarily for adrenal insufficiency can be included provided they meet exacerbation inclusion criteria]
- Other ongoing immunosuppressive/ immunomodulating therapy [e.g. methotrexate, ciclosporine, azathioprine] other than oral corticosteroids for asthma.
- Bronchial thermoplasty conducted within 6 months of Visit 1.
- History of known immunodeficiency disorder including a previous positive human immunodeficiency virus (HIV) test
- Active or suspected Helminth infection. Patients with helminth infections must be excluded until the infection has been treated
- Known hypersensitivity to benralizumab (the active substance) or any of the excipients [Histidine, Histidine hydrochloride monohydrate, Trehalose dihydrate, Polysorbate 20, water for injections]
- Women of child bearing potential (WoCBP) who are not willing to use highly effective contraception during treatment with benralizumab and for 16 weeks after the last dose. WoCBP will be required to undergo a urine pregnancy test prior to administration of each benralizumab injection.
- Current malignancy, or history of malignancy, except for:
- patients who have had non-melanoma skin cancers or in situ carcinoma of the cervix - these patients are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent is obtained. b) Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent is obtained.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United Kingdom15 sites
Belfast City Hospital
Belfast
Birmingham Heartlands Hospital
Birmingham
Bradford Royal Infirmary
Bradford
Gartnavel General Hospital
Glasgow
Castle Hill Hospital
Hull
Glenfield Hospital
Leicester
Royal Liverpool University Hospital
Liverpool
Guy's and St Thomas's Hospital
London
Royal Brompton Hospital
London
Royal Free Hospital
London
Wythenshawe Hospital
Manchester
Freeman Hospital
Newcastle
Churchill Hospital
Oxford
Queen Alexandra Hospital
Portsmouth
Southampton General Hospital
Southampton
About this study
Official title: Asthma Exacerbation Profile in Patients on Open Label Treatment With Benralizumab for Severe Eosinophilic Asthma - an Exploratory Cohort Study
This is an exploratory study, the focus of which is to understand the nature of asthma exacerbations that occur despite open label benralizumab therapy in severe eosinophilic asthma.
Read the detailed description
A phase IV, open-label, prospective, multi-centre cohort study in patients with severe eosinophilic asthma (Global Initiative for Asthma [GINA] steps 4 and 5 classification of asthma severity) who will be treated with benralizumab injections. The study is exploratory and will assess deteriorations in asthma control (exacerbations) to characterise the clinical severity of each exacerbation and the airway and systemic inflammatory phenotype associated with these events. Clinical assessment and management of each exacerbation will be in line with standard clinical guidelines. 150 participants will be recruited and receive treatment for either 56 or 80 weeks.
- Conditions
- Asthma
- Being tested
- Benralizumab
- Keywords
- benralizumab, exacerbation, eosinophilic
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenralizumabDrug
subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Other | Benralizumab 30mg by subcutaneous injection, 18 months treatment for the first 75 participants enrolled, 12 months treatment for participants 76-150 Receives: Drug: Benralizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood eosinophil counts during a clinical deterioration whilst on benralizumab
Measured: up to 56 or 80 weeks
Fall in lung function, as measured by FEV1, during a clinical deterioration whilst on benralizumab.
Measured: up to 56 or 80 weeks
Change in asthma symptom scores during a clinical deterioration whilst on benralizumab.
Measured: up to 56 or 80 weeks
The number of patients progressing to rescue oral corticosteroids during a clinical deterioration whilst on benralizumab.
Measured: up to 56 or 80 weeks
Secondary outcomes (14)
Measurement of the magnitude of response to benralizumab - oral steroid reduction with benralizumab at 56 weeks
proportion of patients who reduce high dose steroid courses and/or maintenance steroid dose by >=25%, 50%, 75% and 100%
Measured: 56 weeks
Measurement of the magnitude of response to benralizumab - numbers of participants with and early and final good response
Early (16/24 weeks): A GETE response of 'good' or 'excellent' to treatment with benralizumab as determined by the study physician. Final (one year): defined as a reduction of high dose corticosteroid courses by >=50% compared to the previous year and/or reduction of maintenance oral steroid dose by >=50%
Measured: 16, 24 weeks, 1 year
Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline
FBC to include Blood eosinophils, sputum eosinophils, blood neutrophil counts
Measured: 16, 56 weeks
Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline
Measurement of exhaled nitric oxide
Measured: 16, 56 weeks
Measurement of the magnitude of response to benralizumab - change in lung function, as measured by FEV1, at 16, 24 and 56 weeks compared to baseline
FEV1 post salbutamol on spirometry and FEV1 in daily diary
Measured: 16, 24 and 56 weeks
Measurement of the magnitude of response to benralizumab - change in lung function at 16, 24 and 56 weeks compared to baseline
peak expiratory flow from the daily electronic meter
Measured: 16, 24 and 56 weeks
Measurement of the magnitude of response to benralizumab - change in patient reported outcomes at 16,24 and 56 weeks compared to baseline
Completion of health outcome questionnaires
Measured: 16, 24 and 56 weeks
Identifying predictors of treatment response
Patients will be classified into treatment responders and non-responders. Logistic regression will be used to identify the predictive value of improvement in early clinical response indicators at 16 weeks on 12 month treatment response.
Measured: 16 weeks and 1 year
Comparing patient reported outcome measures
Correlation of completed questionnaires: Scores, and changes in scores, from the SAQ will be correlated with the SGRQ and mini-AQLQ. The SAQ score will be evaluated against demographic features at baseline.
Measured: 16, 24 and 56 weeks
Onset of clinical response
Time to first exacerbation and change in FEV1 with time.
Measured: up to 56 or 80 weeks
Exploratory Microbiomics
Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response
Measured: baseline, 4, 16 and 56 weeks, during exacerbation visits
Exploratory viromics
Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response
Measured: baseline, 4, 16 and 56 weeks, during exacerbation visits
Exploratory transcriptomics
Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response
Measured: baseline, 4, 16 and 56 weeks, during exacerbation visits
Exploratory biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways
Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response
Measured: baseline, 4, 16 and 56 weeks, during exacerbation visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start30 Sep 2019
- Primary completion22 Feb 2024
- Study completion23 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, AstraZeneca, Queen's University, Belfast, Bosch Healthcare Solutions GmbH, InHealthcare, University of Leicester, University of Plymouth, Vitalograph
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04102800
- Sponsor's protocol ID
- GN17RM684
- Acronym
- BenRex
- Status last verified
- Apr 2024
- First submitted
- 12 Mar 2019
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Butler CA, Heaney LG. Fractional exhaled nitric oxide and asthma treatment adherence. Curr Opin Allergy Clin Immunol. 2021 Feb 1;21(1):59-64. doi: 10.1097/ACI.0000000000000704.
PubMed 33369570
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Asthma Exacerbation Profile in Patients on Open Label Treatment With Benralizumab for Severe Eosinophilic Asthma - an Exploratory Cohort Study
- ClinicalTrials.gov ID
- NCT04102800
- Acronym / sponsor ID
- BenRex / GN17RM684
- Conditions
- Asthma
- Keywords
- benralizumab, exacerbation, eosinophilic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow, AstraZeneca, Queen's University, Belfast, Bosch Healthcare Solutions GmbH, InHealthcare, University of Leicester, University of Plymouth, Vitalograph
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 22 Feb 2024 (actual)
- Study completion
- 23 Apr 2024 (actual)
- First posted
- 25 Sep 2019 (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.
This is an exploratory study, the focus of which is to understand the nature of asthma exacerbations that occur despite open label benralizumab therapy in severe eosinophilic asthma.
Detailed description
A phase IV, open-label, prospective, multi-centre cohort study in patients with severe eosinophilic asthma (Global Initiative for Asthma [GINA] steps 4 and 5 classification of asthma severity) who will be treated with benralizumab injections. The study is exploratory and will assess deteriorations in asthma control (exacerbations) to characterise the clinical severity of each exacerbation and the airway and systemic inflammatory phenotype associated with these events. Clinical assessment and management of each exacerbation will be in line with standard clinical guidelines. 150 participants will be recruited and receive treatment for either 56 or 80 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Other | Drug: BenralizumabBenralizumab 30mg by subcutaneous injection, 18 months treatment for the first 75 participants enrolled, 12 months treatment for participants 76-150 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- able and willing to provide written informed consent and to comply with the study protocol, including being able to attend for assessment during a symptomatic deterioration
- severe asthma confirmed after assessment by an asthma specialist, requiring treatment with high dose inhaled corticosteroids (ICS) as per BTS criteria [>1000 fluticasone proportionate equivalent] and >1 additional drug for asthma (e.g. long acting beta 2 antagonist (LABA)/leukotriene receptor antagonist/theophylline/long acting muscarinic antagonist) at screening [participants may be included with a lower dose of current ICS at the discretion of the investigator if previous high ICS dose had led to side effects]
- Adherent with background asthma medication in the opinion of the investigator [adherence assessments as per local practice]
- Assessed and treatment optimised for any significant asthma-related co-morbidities
- Considered suitable by an asthma specialist for treatment with a monoclonal antibody to block the Interleukin-5 pathway as per local practice. Participants will have: a) recorded blood eosinophil count ≥0.3 x 109/L within the past year along with a history of either ≥4 asthma exacerbations requiring high dose oral corticosteroids* and/or maintenance systemic corticosteroids equivalent to prednisolone ≥5 mg/day for 6 months or longer OR b) recorded blood eosinophil count ≥0.4 x 109/L within the past year along with a history of ≥ 3 asthma exacerbations requiring high dose oral corticosteroids*
Key exclusion criteria (19 listed)
- Acute exacerbation requiring high dose oral corticosteroids in the 2 weeks prior to Visit 1 or during the screening period. Such patients would be re-assessed after 2 weeks for re-screening.
- Other clinically significant medical disease or uncontrolled concomitant disease that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study.
- History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.
- Female patients who are pregnant or lactating or planning a family
- Active lung disease other than asthma [Note: Controlled obstructive sleep apnoea (OSA), minor bronchiectasis, asbestos pleural plaques or old (inactive) TB scars are not exclusion criteria]. Patients where an asthma-COPD overlap is suspected by the investigator are not eligible for inclusion.
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 |
|---|---|---|
| Benralizumabsubcutaneous injection | Drug | Treatment |
Primary outcome
Blood eosinophil counts during a clinical deterioration whilst on benralizumab
Time frame: up to 56 or 80 weeks
Fall in lung function, as measured by FEV1, during a clinical deterioration whilst on benralizumab.
Time frame: up to 56 or 80 weeks
Change in asthma symptom scores during a clinical deterioration whilst on benralizumab.
Time frame: up to 56 or 80 weeks
The number of patients progressing to rescue oral corticosteroids during a clinical deterioration whilst on benralizumab.
Time frame: up to 56 or 80 weeks
14 secondary outcomes
Measurement of the magnitude of response to benralizumab - oral steroid reduction with benralizumab at 56 weeks
Time frame: 56 weeks
Measurement of the magnitude of response to benralizumab - numbers of participants with and early and final good response
Time frame: 16, 24 weeks, 1 year
Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline
Time frame: 16, 56 weeks
Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline
Time frame: 16, 56 weeks
Measurement of the magnitude of response to benralizumab - change in lung function, as measured by FEV1, at 16, 24 and 56 weeks compared to baseline
Time frame: 16, 24 and 56 weeks
Measurement of the magnitude of response to benralizumab - change in lung function at 16, 24 and 56 weeks compared to baseline
Time frame: 16, 24 and 56 weeks
Measurement of the magnitude of response to benralizumab - change in patient reported outcomes at 16,24 and 56 weeks compared to baseline
Time frame: 16, 24 and 56 weeks
Identifying predictors of treatment response
Time frame: 16 weeks and 1 year
Comparing patient reported outcome measures
Time frame: 16, 24 and 56 weeks
Onset of clinical response
Time frame: up to 56 or 80 weeks
Exploratory Microbiomics
Time frame: baseline, 4, 16 and 56 weeks, during exacerbation visits
Exploratory viromics
Time frame: baseline, 4, 16 and 56 weeks, during exacerbation visits
Exploratory transcriptomics
Time frame: baseline, 4, 16 and 56 weeks, during exacerbation visits
Exploratory biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways
Time frame: baseline, 4, 16 and 56 weeks, during exacerbation visits
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Derived from this study: PubMed 33369570Butler CA, Heaney LG. Fractional exhaled nitric oxide and asthma treatment adherence. Curr Opin Allergy Clin Immunol. 2021 Feb 1;21(1):59-64. doi: 10.1097/ACI.0000000000000704.
- Individual participant dataSharing planned: No
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Asthma
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.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Benralizumab in people with Asthma, run by NHS Greater Glasgow and Clyde at 15 sites in United Kingdom.
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 6 inclusion and 19 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: finished, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood eosinophil counts during a clinical deterioration whilst on benralizumab (time frame: up to 56 or 80 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04102800, which also lists 1 linked publication.
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 25 Apr 2024.