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

Phase 3RecruitingNCT06750289

AstraZeneca400 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

400

Conditions

Eosinophilic Asthma

Interventions

Eligibility

Sex: ALLMin age: 12 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (160)

Research Site

Chandler, Arizona, United States

WITHDRAWN

Research Site

Sun City, Arizona, United States

RECRUITING

Research Site

Tucson, Arizona, United States

RECRUITING

Research Site

Bakersfield, California, United States

Outcomes

Primary Outcomes

Annualized asthma exacerbation rate

To assess asthma exacerbation rate.

Time frame: Baseline through Week 48

Secondary Outcomes

Change in Saint George's Respiratory Questionnaire (SGRQ) total score

The SGRQ is a 50-item ePRO instrument developed to measure the health status of participants with airway obstruction disease. The questionnaire is divided into 2 parts: Part 1 consists of 8 items that pertain to the severity of respiratory symptoms in the preceding 4 weeks, and Part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and 3 component scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score ranges from 0 to 100 with 0 indicating the best possible health status and 100 representing the worst possible health status

Time frame: Baseline through Week 48

Change in pre-bronchodilator FEV1

Lung function is assessed by FEV1 which was measured by spirometry. Spirometry will be performed by the Investigator or authorized delegate according to American Thoracic Society /European Respiratory Society guidelines.

Time frame: Baseline through Week 48

Change in Asthma control questionnaire (ACQ) scale score.

The ACQ-6 is a shortened version of the full 7-item ACQ questionnaire, which assesses asthma symptoms (nighttime awakening, symptoms on awakening, activity limitation, shortness of breath, wheezing, SABA use) but omits the FEV1 measurement from the original ACQ-7 assessment. Participants are asked to recall how their asthma has been during the previous week by responding to 6 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The total ACQ-6 score is the mean of the responses. The effect of benralizumab will be evaluated with the change from baseline in ACQ-6 to End of treatment (week 48) and over the treatment period.

Time frame: Baseline through Week 48.

Time to first asthma exacerbation

Time to the first occurrence of asthma exacerbation post randomisation.

Time frame: Baseline through Week 48.

Annualized asthma exacerbation rate associated with an emergency/urgent care visit or a hospitalization

The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator that are associated with an emergency room/urgent care visit or a hospitalization adjusted by the time of follow-up.

Time frame: Baseline through Week 48.

Number and proportion of participants that meet each component of a 4-component clinical remission composite

* Number and proportion of participants that meet each component of a 4-component clinical remission composite (no exacerbations; no mOCS use; ACQ-6 \< 1.5); and stable FEV1 (defined as change from baseline in FEV1 \> -100 mL) at Week 24 and EOT. * Number and proportion of participants that meet 0, 1, 2, 3 and all 4 components of the composite remission endpoint at Week 24 and EOT.

Time frame: Week 24 and Week 48.

Safety Adverse Event (AEs), Serious Adverse Event (SAEs), Adverse event leading to treatment discontinuation (DAEs.)

Time frame: Baseline through Week 48.

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

Overview

Conditions

Interventions

Eligibility

Locations (160)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts