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Benralizumab Exacerbation Study (BenRex)

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ClinicalTrials.gov Identifier: NCT04102800
Recruitment Status : Recruiting
First Posted : September 25, 2019
Last Update Posted : July 12, 2021
Sponsor:
Collaborators:
University of Glasgow
AstraZeneca
Queen's University, Belfast
Bosch Healthcare Solutions GmbH
InHealthcare
University of Leicester
University of Plymouth
Vitalograph
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Brief 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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Benralizumab Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Asthma Exacerbation Profile in Patients on Open Label Treatment With Benralizumab for Severe Eosinophilic Asthma - an Exploratory Cohort Study
Actual Study Start Date : September 30, 2019
Estimated Primary Completion Date : March 31, 2024
Estimated Study Completion Date : May 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Treatment
Benralizumab 30mg by subcutaneous injection, 18 months treatment for the first 75 participants enrolled, 12 months treatment for participants 76-150
Drug: Benralizumab
subcutaneous injection




Primary Outcome Measures :
  1. Blood eosinophil counts during a clinical deterioration whilst on benralizumab [ Time Frame: up to 56 or 80 weeks ]
  2. Fall in lung function, as measured by FEV1, during a clinical deterioration whilst on benralizumab. [ Time Frame: up to 56 or 80 weeks ]
  3. Change in asthma symptom scores during a clinical deterioration whilst on benralizumab. [ Time Frame: up to 56 or 80 weeks ]
  4. The number of patients progressing to rescue oral corticosteroids during a clinical deterioration whilst on benralizumab. [ Time Frame: up to 56 or 80 weeks ]

Secondary Outcome Measures :
  1. Measurement of the magnitude of response to benralizumab - oral steroid reduction with benralizumab at 56 weeks [ Time Frame: 56 weeks ]
    proportion of patients who reduce high dose steroid courses and/or maintenance steroid dose by >=25%, 50%, 75% and 100%

  2. 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 ]
    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%

  3. Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline [ Time Frame: 16, 56 weeks ]
    FBC to include Blood eosinophils, sputum eosinophils, blood neutrophil counts

  4. 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 exhaled nitric oxide

  5. 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 ]
    FEV1 post salbutamol on spirometry and FEV1 in daily diary

  6. 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 ]
    peak expiratory flow from the daily electronic meter

  7. 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 ]
    Completion of health outcome questionnaires

  8. Identifying predictors of treatment response [ Time Frame: 16 weeks and 1 year ]
    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.

  9. Comparing patient reported outcome measures [ Time Frame: 16, 24 and 56 weeks ]
    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.

  10. Onset of clinical response [ Time Frame: up to 56 or 80 weeks ]
    Time to first exacerbation and change in FEV1 with time.

  11. Exploratory Microbiomics [ Time Frame: baseline, 4, 16 and 56 weeks, during exacerbation visits ]
    Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response

  12. Exploratory viromics [ Time Frame: baseline, 4, 16 and 56 weeks, during exacerbation visits ]
    Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response

  13. Exploratory transcriptomics [ Time Frame: baseline, 4, 16 and 56 weeks, during exacerbation visits ]
    Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response

  14. Exploratory biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways [ Time Frame: baseline, 4, 16 and 56 weeks, during exacerbation visits ]
    Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response


Other Outcome Measures:
  1. Validation of home spirometry with video supported tests [ Time Frame: Baseline, 2 and 24 weeks ]
    Comparison of spirometry done on site with another done off site with video support from the study team.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Treatment with any of the following prior to Visit 1 or during the study

    1. any biologic medicine for asthma or an immunomodulating biologic agent for other conditions in the 3 months prior to Visit 1
    2. an investigational agent within 30 days of Visit 1 (or five half lives of the investigational agent, whichever is longer).
    3. Administration of live attenuated vaccine 30 days prior to Visit 1. Other types of approved vaccines are allowed.
    4. 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]
    5. 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:

    1. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04102800


Contacts
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Contact: Rekha Chaudhuri, MD MBBS 0044 141 211 0095 rekha.chaudhuri@ggc.scot.nhs.uk
Contact: Lynsey Gillespie, PhD 0141 314 4363 lynsey.gillespie@ggc.scot.nhs.uk

Locations
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United Kingdom
Belfast City Hospital Not yet recruiting
Belfast, United Kingdom
Contact: Liam Heaney       l.heaney@qub.ac.uk   
Birmingham Heartlands Hospital Not yet recruiting
Birmingham, United Kingdom
Contact: Adel Mansur       adel.mansur@heartofengland@nhs.uk   
Bradford Royal Infirmary Not yet recruiting
Bradford, United Kingdom
Contact: Dinesh Saralaya       dinesh.saralaya@bthft.nhs.uk   
Addenbrooke's Hospital Not yet recruiting
Cambridge, United Kingdom
Contact: Shuaib Nasser       shuaib.nasser@addenbrookes.nhs.uk   
Gartnavel General Hospital Recruiting
Glasgow, United Kingdom
Contact: Nicola Lee       nicola.lee@ggc.scot.nhs.uk   
Contact: Steven Smith       steven.smith@ggc.scot.nhs.uk   
Glenfield Hospital Not yet recruiting
Leicester, United Kingdom
Contact: Salman Siddiqui       ss338@leicester.ac.uk   
Royal Liverpool University Hospital Not yet recruiting
Liverpool, United Kingdom
Contact: Hassan Burhan       hassan.burhan@rlbuht.nhs.uk   
Guy's and St Thomas's Hospital Not yet recruiting
London, United Kingdom
Contact: David Jackson       david.jackson@gstt.nhs.uk   
St Bartholomew's Hospital Not yet recruiting
London, United Kingdom
Contact: Paul Pfeffer         
Wythenshawe Hospital Not yet recruiting
Manchester, United Kingdom
Contact: Stephen Fowler       stephen.fowler@manchester.ac.uk   
Freeman Hospital Not yet recruiting
Newcastle, United Kingdom
Contact: James Lordan       j.lordan@nhs.net   
Churchill Hospital Not yet recruiting
Oxford, United Kingdom
Contact: Ian Pavord       ian.pavord@ndm.ox.ac.uk   
Queen Alexandra Hospital Not yet recruiting
Portsmouth, United Kingdom
Contact: Thomas Brown       thomas.brown@porthosp.nhs.uk   
Southampton General Hospital Not yet recruiting
Southampton, United Kingdom
Contact: Ramesh Kurukulaaratchy         
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
AstraZeneca
Queen's University, Belfast
Bosch Healthcare Solutions GmbH
InHealthcare
University of Leicester
University of Plymouth
Vitalograph
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT04102800    
Other Study ID Numbers: GN17RM684
First Posted: September 25, 2019    Key Record Dates
Last Update Posted: July 12, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NHS Greater Glasgow and Clyde:
benralizumab
exacerbation
eosinophilic
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents