Clinical Trial Results:
Asthma Exacerbation Profile in patients on open label treatment with Benralizumab for severe eosinophilic asthma - an exploratory cohort study
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Summary
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EudraCT number |
2018-003699-11 |
Trial protocol |
GB |
Global end of trial date |
23 Apr 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Aug 2026
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First version publication date |
13 Aug 2026
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GN17RM684
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04102800 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
NHS Greater Glasgow and Clyde
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Sponsor organisation address |
1055 Great Western Road, Glasgow, United Kingdom, G12 0XH
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Public contact |
Dr Lynsey Gillespie , NHS Greater Glasgow and Clyde, 0044 (0)141 201 9316 , Lynsey.Gillespie@ggc.scot.nhs.uk
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Scientific contact |
Dr Lynsey Gillespie , NHS Greater Glasgow and Clyde, 0044 (0)141 201 9316 , Lynsey.Gillespie@ggc.scot.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Mar 2026
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Apr 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Apr 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the inflammatory and physiological characteristics of an asthma exacerbation whilst on treatment with benralizumab for severe eosinophilic asthma.
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Protection of trial subjects |
All investigators and key trial personnel will complete GCP training.
PI at each site will assign tasks to staff to the Delegation log depending on their skills and training.
Correct Inclusion of participants - A delegated study doctor will sign off the check of inclusion and exclusion criteria prior to administration of the study drug.
Investigational drug - The drug is benralizumab, which is licensed in Europe and is being used in its licensed indication with no change in dose or regimen in this study. The risk is no greater than using other clinically available monoclonal antibodies for asthma.
The risk of anaphylaxis is very unlikely as no cases were recorded in clinical trials, but will advise patients of symptoms of anaphylaxis and have emergency medication available at sites.
Patients will be asked to wait at site for observation for at least 2 hours after the first injection and 1 hour after the next 3 injections.
Hypersensitivity reactions - have occurred following administration of benralizumab. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e. days). In the event of a hypersensitivity reaction that the PI records as benralizumab related the drug will be discontinued.
All AE’s will be collected and reported as per protocol.
A Drug Safety Monitoring Committee is not planned as it is a Phase 4 study of a licensed medication and the known risk in terms of expected serious adverse events is not significant. The Trial Management Group and Trial Steering Committees will monitor safety.
AE’s will be collected for up to 3 months after the last study injection.
Study procedures: Blood tests, spirometry - All procedures will be carried out by trained staff. Potential risks of procedures will be outlined in the patient information sheet. There is no particularly invasive procedure in this study.
Induced sputum Hypertonic saline will be used if the baseline FEV1 is above 50% predicted and 1L
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Background therapy |
participants own asthma treatment - high dose inhaled corticosteroid + 1 other additional drug for asthma (e.g. long acting beta2 agonist (LABA), leukotriene receptor antagonist (LTRA) such as montelukast, theophylline, long acting muscarinic antagonist (LAMA) such as tiotropium). | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
30 Sep 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 156
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Worldwide total number of subjects |
156
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
122
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From 65 to 84 years |
34
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were identified from severe asthma clinics across the UK at 15participating sites from 30th Sept 2019 unto 2nd Dec 2022 | |||||||||
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Pre-assignment
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Screening details |
Informed consent was obtained at the screening visit for 176 participants. 157 were enrolled and had Baseline assessments included spirometry, induced sputum, FeNO, full blood count [FBC] and asthma- related questionnaires. After a two-week run-in period, 156 participants started open-label benralizumab [Fasenra®] 30mg via subcutaneous injection. | |||||||||
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Period 1
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Period 1 title |
Baseline and final Analysis (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
N/A
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treatment Arm - Experienced an exacerbation | |||||||||
Arm description |
Benralizumab | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Benralizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in dose-dispenser cartridge
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Benralizumab 30mg by subcutaneous injection every 4 weeks for the first 3 doses and then every 8 weeks thereafter.
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Arm title
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Treatment Arm - Did not experience an exacerbation | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Benralizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in dose-dispenser cartridge
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Benralizumab 30mg by subcutaneous injection every 4 weeks for the first 3 doses and then every 8 weeks thereafter.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline and final Analysis
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Primary endpoint - Experienced an exacerbation
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Total analysis - Primary endpoint - To assess the inflammatory [blood cell counts, exhaled nitric oxide] and physiological [FEV1, ACQ-6] characteristics of an asthma exacerbation whilst on treatment with benralizumab for severe eosinophilic asthma.
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Subject analysis set title |
Primary endpoint - Did not experience an exacerbation
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Total analysis - Primary endpoint - To assess the inflammatory [blood cell counts, exhaled nitric oxide] and physiological [FEV1, ACQ-6] characteristics of an asthma exacerbation whilst on treatment with benralizumab for severe eosinophilic asthma.
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End points reporting groups
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Reporting group title |
Treatment Arm - Experienced an exacerbation
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Reporting group description |
Benralizumab | ||
Reporting group title |
Treatment Arm - Did not experience an exacerbation
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Reporting group description |
- | ||
Subject analysis set title |
Primary endpoint - Experienced an exacerbation
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Total analysis - Primary endpoint - To assess the inflammatory [blood cell counts, exhaled nitric oxide] and physiological [FEV1, ACQ-6] characteristics of an asthma exacerbation whilst on treatment with benralizumab for severe eosinophilic asthma.
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Subject analysis set title |
Primary endpoint - Did not experience an exacerbation
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Total analysis - Primary endpoint - To assess the inflammatory [blood cell counts, exhaled nitric oxide] and physiological [FEV1, ACQ-6] characteristics of an asthma exacerbation whilst on treatment with benralizumab for severe eosinophilic asthma.
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End point title |
To study the nature of asthma exacerbation events while on treatment with benralizumab - FeNO | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Between September 30th 2019 to April 23rd Apr 2024
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Statistical analysis title |
Change from stable on IMP to first exacerbation | |||||||||||||||
Comparison groups |
Treatment Arm - Experienced an exacerbation v Treatment Arm - Did not experience an exacerbation
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Number of subjects included in analysis |
156
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||||||||
P-value |
= 0.014 | |||||||||||||||
Method |
Regression, Linear | |||||||||||||||
Parameter type |
Median difference (final values) | |||||||||||||||
Confidence interval |
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| Notes [1] - Baseline |
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Adverse events information
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Timeframe for reporting adverse events |
September 8 30th 2019 and April 23rd 2024
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
28
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Reporting groups
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Reporting group title |
Adverse events - SAEs and ARs
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Nov 2019 |
Discrepancy in the PIS/ICF revised to reflect that the name and telephone number of participants is provided for the purposes of the electronic diary. |
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14 Apr 2020 |
Changes needed in line with the current COVID-19 pandemic to limit attendance at hospital sites
Patients will continue to receive benralizumab injections in the study. The device will change from the pre-filled
syringe to an auto-injector during this period and patients taught to self-inject so that they will not need to attend
hospital during the COVID crisis. Patients will receive the same dose / formulation in the pen device.
Patients will not be attending for study visits so only limited study data can be collected during this period. This will
be collected via phone with the patient in line with the visit schedule of assessments. Patients will be advised not to
attend for exacerbations visits. At present there are a limited number of patients in the study so although some of the
data will be missed this is expected to have a minimal effect on the overall study. The study statistician has reviewed
and agreed the changes. |
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21 Oct 2020 |
Changes to reduce the onsite visits. Handheld devices provided to patients to allow measurements and sample collection to be done off site for some visits. Key study visits will still be conducted onsite but samples can be collected prior to attending. Selected study visits will be conducted with the study team via video call. Patients will be provided with handheld Spirometer and vivatmo me devices and consumables for collection of samples.
In line with changes to routine practice, option for participants to switch from study specific benralizumab supplies to usual local NHS supply arrangements for benralizumab which includes use of homecare services. To facilitate participant self-administration, participants will now be provided with pre-filled pen presentation.
Handheld devices to be purchased/ donated and provided for patient use at home. Exacerbation kits and sample consumable will be provided to patients to allow for sample collection off site where appropriate.
Study recruitment was suspended due to the COVID-19 pandemic. The duration of the study will be extended by 10 months, with the agreement of the funder, to allow for the delay. Given that only one of the study sites was open and acively recruiting there should be no resource implications for the other sites.
Patient instructions to be provided to assist with the sample collection and outcome measures by patients at home.
Addition to exclusion: 13. Current malignancy, or history of malignancy, except for:a) 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 |
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07 Apr 2021 |
Minor changes to the protocol for clarification. Addition to the Patient Information Sheet / Informed Consent Form to include collection of patient date of birth. The current electronic diary provider is unable to continue to support the service moving forward and this is needed for the new provider. Addition to the PIS/ICF to include that data, including postcode, will be held by the Robertson Centre, University of Glasgow and that consent forms will be uploaded. Tracked and clean copies of all affected documents, and a summary of the protocol changes, have been included with the submission. |
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08 Jun 2021 |
Minor changes to the protocol and PIS to include clarification on COVID vaccination and considerations in relation to timing and administration of benralizumab where applicable . Clarification in the protocol on reporting of COVID vaccine as a concomitant medication. Addition to the Patient Information Sheet / Informed Consent form to include collection of NHS number. This is needed for initiation of patients into the new electronic diary service. Patient identifiers are already being collected for the purposes of the electronic diary and this has been reviewed and approved by REC previously. Tracked and clean copies of all documents have been included with the submission. |
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21 Jun 2021 |
Minor change to the patient instruction regarding the electronic diary provider. This is due to a change to the service provider and the instructions have been updated in line with the wording used by the new provider. A tracked and clean version of the revised document is attached with the submission. |
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05 Jan 2022 |
Revisions to the protocol to include clarification on the sputum endpoints requested by the Sponsor. Changes to the breathomics sampling timepoints / reduction in number of samples collected. Changes to the inclusion criteria in relation to a new inhaler Enerzair. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
