Efficacy of Reslizumab Dose Escalation in Patients With Severe Asthma and Persistent Sputum Eosinophilia Despite Standard Dose Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Change in Sputum eosinophilia
研究概览
简要总结
Dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.
详细描述
Monoclonal antibody therapies targeting the interleukin-5 (IL-5) pathway, critical for maintaining eosinophil homeostasis, have been developed as adjunct therapy for severe asthma with an eosinophilic phenotype. Reslizumab/Cinqair is an approved/marketed product administered monthly by intravenous to severe eosinophilic asthmatics at 3mg/kg. However some patients do exhibit sputum eosinophilia at this dosage. We are investigating whether those that receive 3mg/kg that have persistent sputum eosinophils would benefit at a higher dose of 4mg/kg and those that still exhibit sputum eosinophils at this elevated dose would show improvement at 5mg/kg.
The overall aim of this study is to determine whether dose escalation of reslizumab can ameliorate sputum eosinophilia in severe asthmatics who have persistent sputum eosinophilia despite treatment with reslizumab at the standard dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Asthma confirmed within the past 2 years by:
- •a. A ≥12% improvement in forced expiratory volume in 1 second (FEV1) after use of a beta agonist, or a methacholine challenge test showing a ≥20% reduction in FEV1 after a concentration of ≤8 mg/mL of methacholine
- •Blood eosinophils ≥400 cells/µL and/or sputum eosinophils ≥3% (or presence of moderate-to-many free eosinophil granules) at the time of study enrollment
- •Treated with an inhaled corticosteroid at a dose of ≥1500 µg of fluticasone propionate (or equivalent) and a long-acting beta agonist with or without oral corticosteroids
- •Ability to provide informed consent
排除标准
- •Current smokers, ex-smokers with greater than 20 pack-year history or ex-smokers who have smoked within the past 6 months
- •Any comorbidity that the investigator believes is a contraindication including but not limited to any respiratory (e.g., chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, pulmonary fibrosis), cardiovascular (e.g., congestive cardiac failure, pulmonary hypertension), hematological, gastrointestinal, immunological, musculoskeletal, infectious, or neoplastic disease
- •Currently treated with another biologic agent (excluding denosumab for osteoporosis)
- •Use of anti-IL-5 (other than reslizumab) or anti-IgE mAb use within the past one month
- •Use of a systemic immunosuppressive or immunomodulatory agent within 6 months prior to study entry
- •Suspected of abusing drugs or alcohol
- •Pregnancy or lactation
结局指标
主要结局
Change in Sputum eosinophilia
时间窗: At baseline and at the end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks.
Absolute difference between the mean sputum eosinophil percent
次要结局
- Change in Number of asthma exacerbations(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in Cumulative systemic corticosteroid dose(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in Blood eosinophil count(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in Type of asthma exacerbations (as determined by quantitative sputum cytometry)(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in Proportion of patients requiring daily oral corticosteroid therapy(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in ACQ5 score(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in FEV1(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)
- Change in Proportion of patients with sputum eosinophils ≤3%(At the start and end of each of three dosing periods (every 16 weeks) for total study duration of 48 weeks)