Benralizumab for Asthma

(BRISOTE Trial)

Recruiting at 139 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: ICS-LABA

Must not be taking: Systemic corticosteroids

Disqualifiers: Pulmonary disease, Chronic infections, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 48 weeks

400 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been on medium-dose ICS-LABA for at least 3 months before starting the trial, so you may need to continue those medications.

What data supports the effectiveness of the drug Benralizumab for asthma?

Research shows that Benralizumab significantly reduces asthma attacks, improves lung function, and enhances quality of life for patients with severe asthma, especially those with high levels of eosinophils (a type of white blood cell). ^{1 2 3 4 5}

Is Benralizumab safe for humans?

Benralizumab has been shown to be generally safe in humans, particularly for those with severe eosinophilic asthma. Studies have documented its safety in reducing asthma exacerbations and improving lung function, with long-term trials confirming its safety over extended periods. ^{1 5 6 7 8}

How is the drug benralizumab different from other asthma treatments?

Benralizumab is unique because it is a monoclonal antibody that targets the interleukin-5 receptor alpha, leading to the rapid depletion of eosinophils (a type of white blood cell involved in inflammation), which significantly reduces asthma exacerbations and improves lung function in patients with severe eosinophilic asthma. ^{2 3 4 5 9}

What is the purpose of this trial?

This study evaluates the efficacy and safety of benralizumab as an add-on therapy in uncontrolled eosinophilic asthma participants treated with medium-dose ICS-LABA compared to the conventional treatment step of escalation of inhaled therapy to high-dose ICS-LABA.

Research Team

Jeremy Cole, MD

Principal Investigator

IPS Research Company

Shahrukh Kureishy, MD

Principal Investigator

Metroplex Pulmonary and Sleep Center

John Zwetchkenbaum, MD

Principal Investigator

Aapri Clinical Research Institute

Erika Gonzalez, MD

Principal Investigator

South Texas Allergy & Asthma Medical Professionals (STAAMP)

Sady Alpizar, MD

Principal Investigator

Clinical Research Trials of Florida, Inc.

Mila Leong, MD

Principal Investigator

Pediatric Pulmonary & Asthma Associates of South Jersey, LLC

Alfonso Gonzalez-Rodriguez, MD

Principal Investigator

Florida Premier Research Institute - Clay Street

Juan Rodriguez, MD

Principal Investigator

Sun City Clinical Research

Neil Kao, MD

Principal Investigator

Allergic Disease & Asthma Center, P.A. (ADAC) - Butler Road Office

Charles Lunn, MD

Principal Investigator

Lynn Health Science Institute East

Tzu-Jen Tzao, MD

Principal Investigator

Pasadena Clinical Trials

Dena Petersen, MD

Principal Investigator

Noble Clinical Research - Elite Clinical Network

Patel Paryus, MD

Principal Investigator

Prime Healthcare - Inglewood

Marvin Heuer, MD

Principal Investigator

Heuer M.D. Research, Inc.

Mina Makaryus, MD

Principal Investigator

Northwell Health - Centers for Advanced Medicine

Sandeep Bansal, MD

Principal Investigator

Clinical Research Associates of Central PA

Muhammad Salim, MD

Principal Investigator

Chandler Clinical Trials

Jose Diaz, MD

Principal Investigator

Flourish Research - Leesburg

Ryan Klein, MD

Principal Investigator

NewportNativeMD, Inc.

Rohit Katial, MD

Principal Investigator

National Jewish Health

Vikas Sayal, MD

Principal Investigator

Henderson Clinical Trials, LLC

Njira Lugogo, MD

Principal Investigator

University of Michigan Health System - A. Alfred Taubman Health Care Center - Pulmonary Clinic

Samuel DeLeon, MD

Principal Investigator

Urban Health Plan

Eligibility Criteria

This trial is for people with a type of asthma called eosinophilic asthma that's not well-controlled by their current medium-dose inhaler treatment. Participants should be adults who can safely receive injections under the skin and have not responded well to standard therapies.

Inclusion Criteria

I've been treated with specific asthma medication for at least 3 months.

Written informed consent

I have asthma treated with a medium or higher dose of inhalers for over a year.

Exclusion Criteria

I have a lung condition other than asthma, or a disease linked to high eosinophil counts.

Any unstable disorder that in the opinion of the investigator could affect the study according to the study protocol

I haven't needed steroids for asthma or antibiotics for infections in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive benralizumab 30 mg SC or placebo as an add-on therapy every 4 weeks for the first 3 doses, then every 8 weeks, for a total of up to 7 injections

48 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Benralizumab

Trial Overview The study is testing if adding Benralizumab, an injectable medication, to current asthma treatment is better than just increasing the dose of inhaled steroids. Some participants will get Benralizumab while others will get a placebo as part of the research.

Participant Groups

Group I: Medium-dose ICS-LABA + benralizumab Active Control 2 Interventions

Participants will be randomised 1:1 to one of the 2 study arms. Participants will receive up to 7 SC injections during study, with the first 3 doses administered every 4 weeks and then subsequent doses every 8 weeks.

Group II: High-dose ICS-LABA + placebo Active Control 2 Interventions

Participants will be randomised 1:1 to one of the 2 study arms. Participants will receive up to 7 SC injections during study, with the first 3 doses administered every 4 weeks and then subsequent doses every 8 weeks.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study of 429 patients with severe eosinophilic asthma treated with benralizumab, asthma exacerbation rates significantly decreased by 52% to 64% after treatment, demonstrating its effectiveness across various eosinophil levels.

Patients switching from other biologics to benralizumab also experienced substantial reductions in exacerbation rates, with 39% to 49% of patients having no exacerbations during the first 24 months of follow-up, indicating long-term clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2. Carstens, D., Maselli, DJ., Mu, F., et al.[2023]

Benralizumab significantly reduces asthma exacerbations and improves lung function in patients with severe, uncontrolled asthma, with a notable reduction in annual exacerbation rates (AER) observed in patients with higher baseline eosinophil counts and more frequent exacerbation histories.

In a pooled analysis of 2295 patients from two phase 3 studies, those receiving benralizumab every 4 weeks showed a 37% reduction in AER compared to placebo, while those receiving it every 8 weeks had a 36% reduction, indicating that the treatment is effective across different eosinophil thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. FitzGerald, JM., Bleecker, ER., Menzies-Gow, A., et al.[2022]

Benralizumab is a monoclonal antibody that targets the interleukin-5 receptor, effectively inhibiting eosinophil and basophil proliferation, which is crucial for managing severe asthma.

Clinical trials have shown that benralizumab significantly reduces asthma exacerbation rates, improves lung function (measured by FEV1), and enhances quality of life for patients with high eosinophil counts, while being well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benralizumab for the treatment of asthma. Matera, MG., Rogliani, P., Calzetta, L., et al.[2018]

In a real-world study of 205 patients with severe eosinophilic asthma treated with benralizumab for an average of 9.8 months, there was a dramatic reduction in exacerbations, with 81% of patients becoming exacerbation-free and a 93.3% decrease in the annualized exacerbation rate.

Benralizumab treatment also led to significant reductions in oral corticosteroid use, with 43.2% of patients able to stop OCS therapy and an overall dose reduction of 56%, indicating its effectiveness in managing severe asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study. Menzella, F., Bargagli, E., Aliani, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Rapid onset of effect of benralizumab on morning peak expiratory flow in severe, uncontrolled asthma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

Benralizumab for the treatment of asthma. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events of benralizumab in moderate to severe eosinophilic asthma: A meta-analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Two-Year Integrated Efficacy And Safety Analysis Of Benralizumab In Severe Asthma. [2022]