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.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 400
- 试验地点
- 161
- 主要终点
- Annualized asthma exacerbation rate
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Benralizumab and placebo will be supplied in identical Accessorised pre-filled syringe (APFS). Medium and high dose ICS-LABA will be supplied in identical inhalers, as appropriate for US and ex-US markets, and the maximum daily dose is the same for the 2 Investigational products (IPs) (2 doses/day).
Participants are not aware of the dose levels to which they are assigned. The Interactive Response Technology / Randomisation and Trial Supply Management (IRT/RTSM) will provide to the investigator(s) or pharmacist(s) the kit identification number to be allocated to the participant at the dispensing visit.
Routines for this will be described in the IRT/RTSM user manual that will be provided to each centre.
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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 V
- •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.
排除标准
- •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.
研究组 & 干预措施
High-dose ICS-LABA + placebo
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.
干预措施: ICS-LABA (Combination Product)
High-dose ICS-LABA + placebo
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.
干预措施: Placebo for Benralizumab (Combination Product)
Medium-dose ICS-LABA + benralizumab
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.
干预措施: ICS-LABA (Combination Product)
Medium-dose ICS-LABA + benralizumab
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.
干预措施: benralizumab (Combination Product)
结局指标
主要结局
Annualized asthma exacerbation rate
时间窗: Baseline through Week 48
To assess asthma exacerbation rate.
次要结局
- Change in Saint George's Respiratory Questionnaire (SGRQ) total score(Baseline through Week 48)
- Change in pre-bronchodilator FEV1(Baseline through Week 48)
- Time to first asthma exacerbation(Baseline through Week 48.)
- Change in Asthma control questionnaire (ACQ) scale score.(Baseline through Week 48.)
- Annualized asthma exacerbation rate associated with an emergency/urgent care visit or a hospitalization(Baseline through Week 48.)
- Number and proportion of participants that meet each component of a 4-component clinical remission composite(Week 24 and Week 48.)
- Safety Adverse Event (AEs), Serious Adverse Event (SAEs), Adverse event leading to treatment discontinuation (DAEs.)(Baseline through Week 48.)