How to "Choosebetweenamab" for Severe Asthma, Comparing Treatment With Mepolizumab and Omalizumab for Patients With Severe Allergic and Eosinophilic Asthma.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- ACQ5
研究概览
简要总结
Mepolizumab is an anti-interleukin-5 ( IL-5) monoclonal antibody that neutralizes IL-5 and reduces eosinophil counts in both sputum and blood. Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody (mAb) used in the treatment of severe allergic eosinophilic asthma
The investigators propose that in patients with the dual phenotypes of severe allergic and eosinophilic asthma, that Mepolizumab is as effective as Omalizumab. However, this trial will also identify key clinical biomarkers that will clarify which patients will respond best to each of these interventions.
This study will be the first direct clinical comparison of these agents and will apply expert clinical characterization, along with cutting edge biotechnology to better inform treatment choices for severe asthma. This is an important and urgent management problem facing the Australian pharmaceutical scheme, where imprecision in prescribing will result in reduced clinical effectiveness as well as substantial and sustained costs.
详细描述
'Choosebetweenamab' will compare active treatment arms (Mepolizumab and Omalizumab) for efficacy and adverse events in a Phase 4, parallel arm, randomized controlled trail setting with computer generated randomization (permuted block randomization, with block sizes of 4 or 6, stratified by baseline eosinophil count using a median split). There is no placebo control. Particpants will not be blinded but masking will be used for people assessing outcomes and analyzing data.
'Chossebetweenamab' will also include a secondary outcome substudy (ISS 11066) to assess biomarkers of efficacy response to treatment using single cell sequencing of peripheral blood cells. Blood samples are taken from the randomized patients in each treatment arm (Mepolizumab and Omalizumab) at baseline and gene expression changes assessed using transcriptomic single cell sequencing of patient white blood cells. The data generated from this will be compared to the clinical outcomes of 'Choosebetweenamab' at all follow-up time points. Single cell gene expression and cell type cluster patterning will be compared to the primary and secondary outcomes to identify baseline predictors (gene and cell type) of treatment efficacy.
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
- Single (Outcomes Assessor)
盲法说明
People assessing outcomes and analyzing results are blinded
入排标准
- 年龄范围
- 12 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a duration of asthma of greater than one year.
- •They must have confirmed asthma defined as: (i) forced expiratory volume (FEV1) reversibility greater than or equal to 12%, and greater than or equal to 200 mL at baseline within 30 minutes after administration of salbutamol (200 to 400 micrograms), or (ii) airway hyperresponsiveness defined as a greater than 20% decline in FEV1 during a direct bronchial provocation test or greater than 15% decline during an indirect bronchial provocation test, or (iii) peak expiratory flow (PEF) variability of greater than 15% between the two highest and two lowest peak expiratory flow rates during 14 days.
- •They must have evidence of poor asthma control despite optimal ICS and long acting beta agonist (LABA), be treated by a respiratory physician or immunologist, and have demonstrated acceptable adherence and inhaler technique. Poor control is defined as: evidence of an FEV1 <80% of predicted in the last year on at least one occasion; treatment with OCS, either daily for at least 6 weeks, or a cumulative dose of OCS of at least 500 mg prednisolone equivalent in the previous 12 months, unless contraindicated or not tolerated.
- •In addition they must demonstrate an: (a) an Asthma Control Questionnaire (ACQ-5)38 score of at least 2.0, as assessed in the previous month, and (b) while receiving optimised asthma therapy in the past 12 months, experienced at least 1 admission to hospital for a severe asthma exacerbation, or 1 severe asthma exacerbation, requiring documented use of OCS initiated or increased for at least 3 days, or parenteral corticosteroids prescribed/supervised by a physician.
- •They must also demonstrate evidence of a dual allergic/ eosinophilic phenotype. This is defined as: a total serum IgE >30IU/mL, past or current evidence of atopy documented by skin prick testing or radioallergosorbent assay, and the participant must have a blood eosinophil count greater than or equal to 300 cells per microlitre in the last 6 weeks.
排除标准
- •Do not fulfil inclusion criteria
- •Unable to attend appointments
- •Significant psychiatric illness
研究组 & 干预措施
Omalizumab
Omalizumab
干预措施: Omalizumab (Drug)
Mepolizumab
Mepolizumab
干预措施: Mepolizumab (Drug)
结局指标
主要结局
ACQ5
时间窗: Assessed after 6 months treatment
The primary outcome will be Asthma control questionairre (ACQ)5, adjusted for baseline ACQ5
次要结局
- Oral corticosteroids(every month up to 6 months after treatment commenced)
- Spirometry(every month up to 6 months after treatment commenced)
- Continuing treatment(6 months post intervention)
- Emergency department presentation(every month up to 6 months after treatment commenced)
- Overall dose of oral corticosteroids(6 months post intervention)
- Adverse events(every month up to 6 months after treatment commenced)
- Exacerbations(every month up to 6 months after treatment commenced)
- Time to first exacerbation reported, by patient or health provider(every month up to 6 months after treatment commenced)
- Hospital admissions(every month up to 6 months after treatment commenced)
- Change in gene expression measured by single cell RNA sequencing of peripheral blood cells (ISS 11066)(Measured prior to treatment and clinical outcomes at 6 months after treatment)
研究者
Professor Peter Wark
Professor and Senior Staff Respiratory Specialist
University of Newcastle, Australia