Benralizumab Initiated During Severe Asthma Attack

Singapore Health Services (SingHealth)

Status and phase: Unknown; Phase 2

Conditions: Asthma Attack; Asthma

Treatments: Drug: Benralizumab 30 MG/ML [Fasenra]; Drug: Placebos

Study type: Interventional

Funder types: Other

Identifiers

NCT04617171

FASTER

Details and patient eligibility

About

Approximately 300 million people have asthma worldwide and 400,000 people died from asthma globally in 2015 (GINA Asthma). Singapore's asthma mortality and hospitalisation rates are several times higher than OECD countries. Spot Blood eosinophil count (BEC) during an acute exacerbation of asthma was a predictor of more severe respiratory failure and was associated with future acute health care utilization (HR 1.8, 95% CI 1.1-2.9, p=0.02) in a previous study conducted across 4 ICUs in Singapore. Benralizumab, an anti-IL5 receptor α monoclonal antibody causes rapid depletion of blood eosinophils and reduces asthma exacerbations when given over 12-month duration in patient with Severe Eosinophilic Asthma. However, the efficacy of Benralizumab when given during an acute exacerbation of asthma in reducing future exacerbations or severity of asthma exacerbation is relatively unexplored. A Phase 2A randomized double-blind placebo-controlled trial involving the use of one dose of the intravenous formulation of Benralizumab (0.3 mg/kg or 1.0mg/kg) in patients presenting with acute asthma exacerbation did not demonstrate difference in the proportion of subjects with >/=1 asthma exacerbation at 12 weeks when compared to placebo (33.3% vs. 38.9%; P=0.67). However, compared with placebo, Benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P=0.01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P=.02) in the combined groups at 12 weeks (secondary outcomes).

Benralizumab, an anti-IL5 receptor α monoclonal antibody causes rapid depletion of blood eosinophils and reduces asthma exacerbations when given over 12-month duration in patient with Severe Eosinophilic Asthma.

This study aims to look at whether subcutaneous administration of Benralizumab when initiated during an acute severe asthma exacerbation and then continued over 48 weeks period can increase time to first exacerbation compared to placebo as well as other key secondary outcome such as hospital readmission and health care utilization.

We hypothesise that administration of Benralizumab when initiated during an acute severe asthma exacerbation and then continued over 48 weeks period can increase time to first exacerbation compared to placebo as well as other key secondary outcome such as hospital readmission and health care utilization.

Full description

The efficacy of Benralizumab when given during an acute exacerbation of asthma in reducing future exacerbations or severity of asthma exacerbation is relatively unexplored. A Phase 2A randomized double-blind placebo-controlled trial involving the use of one dose of the intravenous formulation of Benralizumab (0.3 mg/kg or 1.0mg/kg) in patients presenting with acute asthma exacerbation did not demonstrate difference in the proportion of subjects with >/=1 asthma exacerbation at 12 weeks when compared to placebo (33.3% vs. 38.9%; P=0.67). However, compared with placebo, Benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P=0.01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P=.02) in the combined groups at 12 weeks (secondary outcomes).

The purpose of this study is to look at whether Benralizumab, an anti-IL5 receptor α monoclonal antibody given subcutaneously compared to placebo given subcutaneously, can increase time to first exacerbation, reduce health care utilisation and improve other asthma outcomes in patients presenting with acute severe asthma exacerbation requiring hospitalisation. Randomized double-blind placebo-controlled trial design was chosen to reduce selection bias by randomisation and concealment of allocation, reduce analysis or interobserver ascertainment bias by blinding, and reduce bias introduced by exclusion after randomisation by using Intention- to-treat (ITT) analysis. In addition, biomarker stratified approach using spot BEC < or >/= 300 cells/microL during an acute exacerbation will be used to evaluate its role as a predictive biomarker for response to Benralizumab.

The study aims to recruit 128 patients over a 2-year period at Singapore General Hospital and Changi General Hospital.

Enrollment: 128 estimated patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects with severe asthma exacerbation requiring hospital admission
• Subjects aged 21 to 65 years with a physician diagnosis of asthma for greater than or equal to 1 year
• Subjects with 2 or more exacerbations in the past 12 months
• On maintenance of medium to high dose ICS/LABA (GINA Step 4 and 5) for at least 6 months
• Blood Eosinophil count of ≥ 150 cells/microL at time of admission or ≥ 300 cells/microL documented over the past 52 weeks
• Informed consent obtained

Exclusion criteria

• Subjects with asthma exacerbations who are treated and then discharged from ED within 24 hours
• Subjects with a physician diagnosis of COPD, bronchiectasis
• Smokers > 20 pack years
• Anaphylactic/anaphylactoid reaction presenting with bronchospasm
• Other known causes of eosinophilia besides asthma (e.g. parasitic infection)
• Subjects who are deemed by investigators to have with life expectancy of < 12 months (any cause)
• Subjects who are already on investigational drug or has been participating in another clinical study with an investigational product during the last 6 months
• Female subjects who are pregnant or planning pregnancy. All subjects should refrain from family planning during and 4 months following the last dose. Male subjects should refrain from fathering a child or donating sperm during the study and 4 months following the last dose
• Subjects with known history of allergy or reaction to any component of the investigational product formation
• Subjects with history of primary immunodeficiency
• Subjects who have received Xolair (anti-IgE mAb) within 4 months before randomization
• Subjects who receive immunoglobulin or blood products within 30 days before randomization

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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128 participants in 2 patient groups, including a placebo group

Benralizumab

Experimental group

Description:

Benralizumab 30 mg given in the form of subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks subsequently up till Week 48.

Treatment:

Drug: Benralizumab 30 MG/ML [Fasenra]

Placebo

Placebo Comparator group

Description:

Normal Saline given subcutaneously every 4 weeks for the first three doses, then every 8 weeks subsequently up till Week 48.

Treatment:

Drug: Placebos