Benralizumab Exacerbation Study

NCT04102800 | Completed Phase 4

• 1 other identifier: GN17RM684
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 15

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.

Conditions

Asthma

Keywords

benralizumab; exacerbation; eosinophilic

Outcome Measures

Primary Outcomes (4)

• Blood eosinophil counts during a clinical deterioration whilst on benralizumab

  up to 56 or 80 weeks

• Fall in lung function, as measured by FEV1, during a clinical deterioration whilst on benralizumab.

  up to 56 or 80 weeks

• Change in asthma symptom scores during a clinical deterioration whilst on benralizumab.

  up to 56 or 80 weeks

• The number of patients progressing to rescue oral corticosteroids during a clinical deterioration whilst on benralizumab.

  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

  56 weeks

• Measurement of the magnitude of response to benralizumab - numbers of participants with and early and final good response

  16, 24 weeks, 1 year

• Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline

  16, 56 weeks

• Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline

  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

  16, 24 and 56 weeks

Other Outcomes (1)

• Validation of home spirometry with video supported tests

  Baseline, 2 and 24 weeks

Study Arms (1)

Treatment

OTHER

Benralizumab 30mg by subcutaneous injection, 18 months treatment for the first 75 participants enrolled, 12 months treatment for participants 76-150

Drug: Benralizumab

Interventions

Benralizumab DRUG

subcutaneous injection

Treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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.
• 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.

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator
• AstraZeneca: collaborator
• Queen's University, Belfast: collaborator
• Bosch Healthcare Solutions GmbH: collaborator
• InHealthcare: collaborator
• University of Leicester: collaborator
• University of Plymouth: collaborator
• Vitalograph: collaborator

Study Sites (15)

Belfast City Hospital

Belfast, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Bradford Royal Infirmary

Bradford, United Kingdom

Location

Gartnavel General Hospital

Glasgow, United Kingdom

Location

Castle Hill Hospital

Hull, United Kingdom

Location

Glenfield Hospital

Leicester, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, United Kingdom

Location

Guy's and St Thomas's Hospital

London, United Kingdom

Location

Royal Brompton Hospital

London, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33369570 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: September 25, 2019
• Study Start: September 30, 2019
• Primary Completion: February 22, 2024
• Study Completion: April 23, 2024
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (15)