Status:

COMPLETED

Benralizumab Exacerbation Study

Lead Sponsor:

NHS Greater Glasgow and Clyde

Collaborating Sponsors:

University of Glasgow

AstraZeneca

Conditions:

Asthma

Eligibility:

All Genders

18-80 years

Phase:

PHASE4

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.

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 w...

Eligibility Criteria

Inclusion

  • 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

  • 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
  • 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.

Key Trial Info

Start Date :

September 30 2019

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 23 2024

Estimated Enrollment :

157 Patients enrolled

Trial Details

Trial ID

NCT04102800

Start Date

September 30 2019

End Date

April 23 2024

Last Update

April 25 2024

Active Locations (15)

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Page 1 of 4 (15 locations)

1

Belfast City Hospital

Belfast, United Kingdom

2

Birmingham Heartlands Hospital

Birmingham, United Kingdom

3

Bradford Royal Infirmary

Bradford, United Kingdom

4

Gartnavel General Hospital

Glasgow, United Kingdom