Clinical trial NCT06750289: Randomised Clinical Trial to Investigate Efficacy and Safety of Benralizumab 30 mg SC as an add-on Therapy in Uncontrolled Eosinophilic Asthma Patients Treated With Medium-dose ICS-LABA Compared to Conventional Escalation to High-dose ICS-LABA Treatment
Official title: BRISOTE: A Multicentre, Randomised, Double-Blind, Parallel Group, Active-Controlled, Phase 3b Study to Evaluate the Efficacy and Safety of Benralizumab 30 mg SC in Eosinophilic Asthma Patients Uncontrolled on Medium-Dose Inhaled Corticosteroid Plus Long-acting β2-Agonist.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Eosinophilic Asthma
Keywords: Eosinophilic Asthma;
Benralizumab,
FASENRA,
Medium-Dose Inhaled Corticosteroid,
Long-acting β2-Agonist
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-12-27
Enrollment: 400
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomised 1:1 to one of the following arms:

* Medium-dose ICS-LABA + benralizumab
* High-dose ICS-LABA + placebo (benralizumab)
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This is a randomized, double-blind, active-controlled, parallel group global study designed to investigate the efficacy and safety of adding fixed-dose benralizumab (30 mg), administered subcutaneously (SC) every 4 weeks for the first 3 doses and then every 8 weeks for participants with a history of eosinophilic asthma, who remain uncontrolled on medium-dose Inhaled corticosteroid-Long-acting β2-agonists (ICS-LABA) with or without other asthma controller(s) (with the exception of oral corticosteroids), compared to the conventional treatment step of escalation of inhaled therapy to high-dose ICS-LABA plus placebo (benralizumab).

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Participant must be 12 to 75 years of age
* Documented history of physician-diagnosed asthma requiring treatment with at least medium-dose ICS (\> 250 μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit (V) 1.
* Documented treatment with medium-dose ICS and LABA for at least 3 months prior to Visit 1 with or without additional asthma controllers (excluding oral corticosteroids).
* Weight of ≥ 35 kg.
* Pre-Bronchodilator (BD) Forced expiratory volume in 1 second (FEV1) of ≤ 90% predicted
* Documented at least 2 asthma exacerbations in the 12 months prior to the date of informed consent.
* ACQ-6 score ≥ 1.5 at Visit 1, plus at least once in the run-in period (from V2 to V3) and at V3.
* Evidence of asthma as documented by excessive variability in lung function, as defined in the protocol.
* Peripheral blood eosinophil count of ≥ 150 cells/μL, as defined in the protocol.
* At least 70% compliance with usual asthma controller ICS-LABA during run-in period (from Visit 2 to Visit 3) based on asthma daily diary.

Exclusion Criteria:

* Important pulmonary disease other than asthma at the discretion of the investigator, or ever been diagnosed with pulmonary or systemic disease, other than asthma, which are associated with elevated peripheral eosinophil counts.
* Asthma exacerbation requiring use of Systemic corticosteroids (SCS), or acute upper/lower respiratory infection that requires antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
* Any unstable disorder that in the opinion of the investigator could affect the study according to the study protocol.
* Clinically significant chronic or ongoing active infections requiring systemic treatment (at investigator's discretion)
* Concurrent participation in another clinical study with an IP or a post-authorisation safety study.
* History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
* Current smokers or former smokers with a smoking history ≥ 10 pack-years. Former smokers must have stopped for at least 6 months prior to Visit 1 to be eligible.

Primary outcomes:
measure: Annualized asthma exacerbation rate
timeFrame: Baseline through Week 48
Secondary outcomes:
measure: Change in Saint George's Respiratory Questionnaire (SGRQ) total score
timeFrame: Baseline through Week 48
measure: Change in pre-bronchodilator FEV1
timeFrame: Baseline through Week 48
measure: Change in Asthma control questionnaire (ACQ) scale score.
timeFrame: Baseline through Week 48.
measure: Time to first asthma exacerbation
timeFrame: Baseline through Week 48.
measure: Annualized asthma exacerbation rate associated with an emergency/urgent care visit or a hospitalization
timeFrame: Baseline through Week 48.
measure: Number and proportion of participants that meet each component of a 4-component clinical remission composite
timeFrame: Week 24 and Week 48.
measure: Safety Adverse Event (AEs), Serious Adverse Event (SAEs), Adverse event leading to treatment discontinuation (DAEs.)
timeFrame: Baseline through Week 48.
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Sun City
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Inglewood
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Pasadena
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Cape Coral
country: United States
facility: Research Site
state: Florida
city: Lauderdale Lakes
country: United States
facility: Research Site
state: Florida
city: Leesburg
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Henderson
country: United States
facility: Research Site
state: Nevada
city: Northfield
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: DuBois
country: United States
facility: Research Site
state: Pennsylvania
city: Warwick
country: United States
facility: Research Site
state: Rhode Island
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: McKinney
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Kamloops
country: Canada
facility: Research Site
state: British Columbia
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Windsor
country: Canada
facility: Research Site
state: Ontario
city: Sainte Foy
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Huizhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Qinhuangdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zhengzhou City
country: China
facility: Research Site
city: Bayonne
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: La Tronche
country: France
facility: Research Site
city: Lyon Cedex
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Suresnes
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Villeurbanne
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Cottbus
country: Germany
facility: Research Site
city: Delitzsch
country: Germany
facility: Research Site
city: Geesthacht
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Munchen
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Pok Fu Lam
country: Hong Kong
facility: Research Site
city: Sha Tin
country: Hong Kong
facility: Research Site
city: Ballinasloe
country: Ireland
facility: Research Site
city: Cork
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Moneymore
country: Ireland
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Cagliari
country: Italy
facility: Research Site
city: Catanzaro
country: Italy
facility: Research Site
city: Genoa
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Modena
country: Italy
facility: Research Site
city: Montebelluna
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Lørenskog
country: Norway
facility: Research Site
city: Alcorcón
country: Spain
facility: Research Site
city: Alzira (Valencia)
country: Spain
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barakaldo
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Burgos
country: Spain
facility: Research Site
city: Cáceres
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Jerez de la Frontera
country: Spain
facility: Research Site
city: Lugo
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Marbella
country: Spain
facility: Research Site
city: Marbella
country: Spain
facility: Research Site
city: Mérida
country: Spain
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Aarau
country: Switzerland
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Chorley
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Portsmouth
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Clinical Research Associates of Central PA
name: Sandeep Bansal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chandler Clinical Trials
name: Muhammad Salim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Flourish Research - Leesburg
name: Jose Diaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NewportNativeMD, Inc.
name: Ryan Klein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Rohit Katial, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henderson Clinical Trials, LLC
name: Vikas Sayal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IPS Research Company
name: Jeremy Cole, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Metroplex Pulmonary and Sleep Center
name: Shahrukh Kureishy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aapri Clinical Research Institute
name: John Zwetchkenbaum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: South Texas Allergy & Asthma Medical Professionals (STAAMP)
name: Erika Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Trials of Florida, Inc.
name: Sady Alpizar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric Pulmonary & Asthma Associates of South Jersey, LLC
name: Mila Leong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida Premier Research Institute - Clay Street
name: Alfonso Gonzalez-Rodriguez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan Health System - A. Alfred Taubman Health Care Center - Pulmonary Clinic
name: Njira Lugogo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Urban Health Plan
name: Samuel DeLeon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun City Clinical Research
name: Juan Rodriguez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Allergic Disease & Asthma Center, P.A. (ADAC) - Butler Road Office
name: Neil Kao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lynn Health Science Institute East
name: Charles Lunn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwell Health - Centers for Advanced Medicine
name: Mina Makaryus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pasadena Clinical Trials
name: Tzu-Jen Tzao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Noble Clinical Research - Elite Clinical Network
name: Dena Petersen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Prime Healthcare - Inglewood
name: Patel Paryus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heuer M.D. Research, Inc.
name: Marvin Heuer, MD
role: PRINCIPAL_INVESTIGATOR
References: