Benralizumab Exacerbation Study (BenRex)

May 3, 2022 updated by: NHS Greater Glasgow and Clyde

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Belfast, United Kingdom
      • Birmingham, United Kingdom
      • Bradford, United Kingdom
      • Glasgow, United Kingdom
      • Hull, United Kingdom
      • Leicester, United Kingdom
      • Liverpool, United Kingdom
      • London, United Kingdom
      • London, United Kingdom
      • London, United Kingdom
        • Not yet recruiting
        • Royal Free Hospital
        • Contact:
          • James Brown
      • Manchester, United Kingdom
      • Newcastle, United Kingdom
      • Oxford, United Kingdom
      • Portsmouth, United Kingdom
      • Southampton, United Kingdom
        • Recruiting
        • Southampton General Hospital
        • Contact:
          • Ramesh Kurukulaaratchy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Blood eosinophil counts during a clinical deterioration whilst on benralizumab
Time Frame: up to 56 or 80 weeks
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
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
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
up to 56 or 80 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%
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
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%
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
FBC to include Blood eosinophils, sputum eosinophils, blood neutrophil counts
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 exhaled nitric oxide
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
FEV1 post salbutamol on spirometry and FEV1 in daily diary
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
peak expiratory flow from the daily electronic meter
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
Completion of health outcome questionnaires
16, 24 and 56 weeks
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.
16 weeks and 1 year
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.
16, 24 and 56 weeks
Onset of clinical response
Time Frame: up to 56 or 80 weeks
Time to first exacerbation and change in FEV1 with time.
up to 56 or 80 weeks
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
baseline, 4, 16 and 56 weeks, during exacerbation visits
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
baseline, 4, 16 and 56 weeks, during exacerbation visits
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
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
Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response
baseline, 4, 16 and 56 weeks, during exacerbation visits

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, 2 and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

AstraZeneca
Queen's University, Belfast
University of Plymouth
University of Leicester
University of Glasgow
Bosch Healthcare Solutions GmbH
InHealthcare
Vitalograph

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2019

Primary Completion (Anticipated)

March 31, 2024

Study Completion (Anticipated)

May 31, 2024

Study Registration Dates

First Submitted

March 12, 2019

First Submitted That Met QC Criteria

September 24, 2019

First Posted (Actual)

September 25, 2019

Study Record Updates

Last Update Posted (Actual)

May 4, 2022

Last Update Submitted That Met QC Criteria

May 3, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN17RM684

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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