Acute Exacerbations Treated With BenRAlizumab (The ABRA Study) (ABRA)

Exacerbations of asthma and COPD are an important cause of hospital admission and the main cause of annual winter bed shortages. Despite current guideline treatment with prednisolone, 40% of patients require further treatment, 15% are readmitted and, of those hospitalised, 10% die within 3 months, all by definition treatment failures. The investigators have shown that there are two dominant patterns of airway inflammation in patients presenting with an acute episode: infection associated neutrophilic airway inflammation; and non-infection related eosinophilic airway inflammation. These patterns cannot be distinguished reliably by clinical categories (i.e. asthma or COPD) or a standard clinical assessment but are identified by the peripheral blood eosinophil count. These findings raise important questions that targeted treatment based on the blood eosinophil count would result in more efficient and effective management. However, even in patients with the right pattern of airway inflammation the beneficial effects of prednisolone have to be offset against a high potential for harm, with an estimated the number needed to harm as 5 for every 10 patients treated.

Benralizumab is an interleukin-5 receptor-α monoclonal antibody, injected subcutaneously, which rapidly reduces peripheral blood eosinophils for 90 days with a satisfactory safety profile. Benralizumab treatment at stable state has been shown to increase post-bronchodilator FEV1 and reduce the rates of severe exacerbations in patients with severe eosinophilic asthma and improve lung function in patients with eosinophilic COPD. Benralizumab is an attractive candidate for the acute treatment of eosinophilic exacerbations, without the side-effects of prednisolone. The investigators propose to test the hypothesis that, for participants who have a raised eosinophil count at exacerbation, a single injection of Benralizumab alone or in combination with prednisolone will improve clinical outcomes compared to prednisolone alone. The investigators will also study the effect of prednisolone on symptoms, lung function and quality of life, in an exacerbation when the eosinophil count is not raised.


Study Type: Interventional  (Clinical Trial)
Estimated Enrollment: 158 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Use of Benralizumab, an Interleukin-5 Receptor-α Monoclonal Antibody as Treatment of Acute Exacerbations of Airways Disease
Estimated Study Start Date: October 21, 2019
Estimated Primary Completion Date: July 26, 2021
Estimated Study Completion Date: July 26, 2022

Arms:
- Observational Arm (Standard care Prednisolone 30mg given daily for 5 days to treat an exacerbation)
- Experimental: Interventional Arm - Group 1 (Benralizumab as a single 100mg sub cut injection and oral placebo tablet daily for 5 days)
- Experimental: Intervention Arm - Group 2 (Benralizumab as a single 100mg sub cut injection and oral prednisolone 30mg daily for 5 days)
- Active Comparator: Intervention Arm - Group 3 (Placebo sub cut injection and oral prednisolone 30mg daily for 5 days)