Benralizumab Exacerbation Study

Asthma Clinical Trial

— BenRex  

Official title:

Asthma Exacerbation Profile in Patients on Open Label Treatment With Benralizumab for Severe Eosinophilic Asthma - an Exploratory Cohort Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04102800
• Other study ID #: GN17RM684
• Status: Completed
• Phase: Phase 4
• Start date: September 30, 2019
• Est. completion date: April 23, 2024

Study information

• Verified date: April 2024
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: April 23, 2024
• Est. primary completion date: February 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Benralizumab
subcutaneous injection

Locations

Country	Name	City	State
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Gartnavel General Hospital	Glasgow
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Guy's and St Thomas's Hospital	London
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Queen Alexandra Hospital	Portsmouth
United Kingdom	Southampton General Hospital	Southampton

Sponsors (9)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	AstraZeneca, Bosch Healthcare Solutions GmbH, InHealthcare, Queen's University, Belfast, University of Glasgow, University of Leicester, University of Plymouth, Vitalograph

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Validation of home spirometry with video supported tests	Comparison of spirometry done on site with another done off site with video support from the study team.	Baseline, 2 and 24 weeks
Primary	Blood eosinophil counts during a clinical deterioration whilst on benralizumab		up to 56 or 80 weeks
Primary	Fall in lung function, as measured by FEV1, during a clinical deterioration whilst on benralizumab.		up to 56 or 80 weeks
Primary	Change in asthma symptom scores during a clinical deterioration whilst on benralizumab.		up to 56 or 80 weeks
Primary	The number of patients progressing to rescue oral corticosteroids during a clinical deterioration whilst on benralizumab.		up to 56 or 80 weeks
Secondary	Measurement of the magnitude of response to benralizumab - oral steroid reduction with benralizumab at 56 weeks	proportion of patients who reduce high dose steroid courses and/or maintenance steroid dose by >=25%, 50%, 75% and 100%	56 weeks
Secondary	Measurement of the magnitude of response to benralizumab - numbers of participants with and early and final good response	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
Secondary	Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline	FBC to include Blood eosinophils, sputum eosinophils, blood neutrophil counts	16, 56 weeks
Secondary	Measurement of the magnitude of response to benralizumab - inflammatory markers at 16 and 56 weeks compared to baseline	Measurement of exhaled nitric oxide	16, 56 weeks
Secondary	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	FEV1 post salbutamol on spirometry and FEV1 in daily diary	16, 24 and 56 weeks
Secondary	Measurement of the magnitude of response to benralizumab - change in lung function at 16, 24 and 56 weeks compared to baseline	peak expiratory flow from the daily electronic meter	16, 24 and 56 weeks
Secondary	Measurement of the magnitude of response to benralizumab - change in patient reported outcomes at 16,24 and 56 weeks compared to baseline	Completion of health outcome questionnaires	16, 24 and 56 weeks
Secondary	Identifying predictors of treatment response	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
Secondary	Comparing patient reported outcome measures	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
Secondary	Onset of clinical response	Time to first exacerbation and change in FEV1 with time.	up to 56 or 80 weeks
Secondary	Exploratory Microbiomics	Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response	baseline, 4, 16 and 56 weeks, during exacerbation visits
Secondary	Exploratory viromics	Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response	baseline, 4, 16 and 56 weeks, during exacerbation visits
Secondary	Exploratory transcriptomics	Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response	baseline, 4, 16 and 56 weeks, during exacerbation visits
Secondary	Exploratory biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways	Samples will be stored for later laboratory biomarker measurements. To assess possible biomarkers of response	baseline, 4, 16 and 56 weeks, during exacerbation visits