Benralizumab Initiated During Severe Asthma Attack

NCT04617171 | Unknown Phase 2 FDA Drug

• 1 other identifier: FASTER
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma Attack; Asthma

Outcome Measures

Primary Outcomes (1)

• Time to first exacerbation in patients with a severe asthma exacerbation with raised blood eosinophil count

  Time to first exacerbation requiring either oral corticosteroid (OCS) use and/or an unscheduled visit to the Emergency Department or hospitalization

  Change from baseline (Day 1) to 52 weeks

Secondary Outcomes (12)

• Time to hospital readmission due to asthma exacerbation (Key Secondary outcome)

  Baseline (Day 1) to 52 weeks

• Rate of severe exacerbation (i.e. requiring admission to hospital for asthma exacerbation)

  Baseline (Day 1) to 52 weeks

• Hospital LOS (index admission and subsequent admissions)

  Change from baseline (Day 1) to 52 weeks

• Need for Intensive Care Unit (ICU) admission with/without mechanical ventilation during the index admission

  Baseline (Day 1) to index admission discharge date

• Hospital survival post admission (index admission)

  Baseline (Day 1) to index admission discharge date

Other Outcomes (1)

• Adverse Events

  Change from baseline (Day 1) to 52 weeks

Study Arms (2)

Benralizumab

EXPERIMENTAL

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.

Drug: Benralizumab 30 MG/ML [Fasenra]

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Benralizumab 30 MG/ML [Fasenra] DRUG

Benralizumab/placebo initiated at an acute severe asthma exacerbation, then continued over a period of 48 weeks

Also known as: Fasenra

Benralizumab

Placebos DRUG

Benralizumab/placebo initiated at an acute severe asthma exacerbation, then continued over a period of 48 weeks

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

Singapore General Hospital

Singapore, Foreign, 169856, Singapore

RECRUITING

Related Publications (4)

• Yii ACA, Tay TR, Puah SH, Lim HF, Li A, Lau P, Tan R, Neo LP, Chung KF, Koh MS. Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations. Clin Exp Allergy. 2019 Dec;49(12):1578-1586. doi: 10.1111/cea.13465. Epub 2019 Aug 6.

  PMID: 31310686 RESULT

• Nowak RM, Parker JM, Silverman RA, Rowe BH, Smithline H, Khan F, Fiening JP, Kim K, Molfino NA. A randomized trial of benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, after acute asthma. Am J Emerg Med. 2015 Jan;33(1):14-20. doi: 10.1016/j.ajem.2014.09.036. Epub 2014 Oct 5.

  PMID: 25445859 RESULT

• Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkstrom V, Goldman M; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2115-2127. doi: 10.1016/S0140-6736(16)31324-1. Epub 2016 Sep 5.

  PMID: 27609408 RESULT

• FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, Gilmartin G, Werkstrom V, Aurivillius M, Goldman M; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2128-2141. doi: 10.1016/S0140-6736(16)31322-8. Epub 2016 Sep 5.

  PMID: 27609406 RESULT

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 Officials

• Mariko Koh

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mariko Koh

CONTACT

62223322; mariko.koh.s.y@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: November 5, 2020
• Study Start: June 2, 2021
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: July 23, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)