A Randomized, Double-blind, Placebo-controlled, Mono-center Study to Evaluate the Effects of Mepolizumab on Airway Physiology in Patients With Eosinophilic Asthma: the MEMORY Study
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- mean change from baseline in pre- and post-bronchodilator FVC at visit 10 (week 24) and at time of response
研究概览
简要总结
The purpose of the MEMORY trial is to compare the effects of mepolizumab with Placebo on airway physiology in patients with eosinophilic asthma
详细描述
Asthma with eosinophilic inflammation in the airways and/or blood eosinophilia is associated with clinical severity including the risk of exacerbations and relevant comorbidities (e.g. nasal polyposis). Interleukin-5 (IL-5) is a cytokine essential for eosinophil trafficking and survival. Clinical trials of blocking IL-5 with anti-IL-5 antibodies (mepolizumab and reslizumab) in patients with uncontrolled eosinophilic asthma resulted in an improvement in exacerbation rate and oral corticosteroid use. In some studies with mepolizumab and reslizumab there was a beneficial effect on lung function (FEV1). In addition, many patients described a profound impact on asthma symptoms and quality of life in personal reports which is not uniformly reflected in clinical trials.
The MEMORY trial is the first to primarily evaluate the effect of mepolizumab treatment on pulmonary function in patients with severe eosinophilic asthma. Importantly, using spirometry and bodyplethysmography will allow to evaluate additional parameters beyond FEV1 that more closely mirror the pathophysiological changes and functional aspects of airflow limitation in asthma in real life, e.g. airway resistance, hyperinflation and diffusion capacity. The proposed trial will answer the important questions: if, and if so, which parameters of airway (patho-) physiology as assessed by bodyplethysmography best reflect clinical response to mepolizumab therapy in patients with severe eosinophilic asthma. In addition, the time course to clinical response will be assessed. Equally important, there is only a loose correlation between FEV1 and parameters of asthma control and asthma-related quality of life. This is why another new and important aspect of this trial is to carefully monitor asthma control and asthma quality in life in correlation with lung function changes beyond FEV1. Finally, it is tempting to speculate that the proposed trial will contribute to the question how to best define clinical response to mepolizumab.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.
- •Male or female patients at least 18 years
- •Physician-diagnosis of asthma and evidence of asthma as documented by either reversibility of airflow obstruction (FEV1 ≥ 12% or 200 ml) demonstrated at visit 1 or visit 2 .
- •ICS dose must be ≥ 1000 μg/day BDP or equivalent daily with or without maintenance oral corticosteroids.
- •Treatment in the past 12 months with an additional controller medication for at least 3 successive months, e.g., long-acting beta-2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline.
- •Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 < 80% predicted recorded at Visit 1 or < 90% for patients on oral corticosteroids.
- •An elevated peripheral blood eosinophil level of ≥ 300/µL that is related to asthma or ≥ 150/µL in patients treated with oral corticosteroids as maintenance therapy demonstrated at visit 1 or in the previous 12 months
- •Confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids. For patients receiving maintenance corticosteroids, the corticosteroid treatment for the exacerbations must have been a two-fold increase or greater in the dose.
排除标准
- •Current smokers or former smokers with a smoking history of ≥ 10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked). Patients who have not smoked for ≥ 6 months before visit 1 and have < 10 pack years can be included into the study.
- •Presence of a clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
- •Patients who have received omalizumab [Xolair] within 130 days of Visit
- •Patients who have received any biological to treat inflammatory disease within 5 half-lives of visit 1
研究组 & 干预措施
Mepolizumab
100 mg SC every 4 weeks for 13 injections
干预措施: Mepolizumab (Drug)
Placebo
Amount of Placebo corresponding to mepolizumab dose SC every 4 weeks for 13 injections
干预措施: Placebo (Drug)
结局指标
主要结局
mean change from baseline in pre- and post-bronchodilator FVC at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator forced vital capacity (FVC) at visit 10 (week 24) and at time of response
mean change from baseline in pre- and post-bronchodilator FEV1 at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) at visit 10 (week 24) and at time of response
mean change from baseline in pre- and post-bronchodilator RV at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator residual volume (RV) at visit 10 (week 24) and at time of response
mean change from baseline in pre- and post-bronchodilator TLC at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator total lung capacity (TLC) at visit 10 (week 24) and at time of response
mean change from baseline in pre- and post-bronchodilator airway resistance at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator airway resistance at visit 10 (week 24) and at time of response
mean change from baseline in pre- and post-bronchodilator IC at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator inspiratory capacity (IC) at visit 10 (week 24) and at time of response
mean change from baseline in pre- and post-bronchodilator CO diffusion capacity at visit 10 (week 24) and at time of response
时间窗: week 24 and time of response
The primary outcome is the mean change from baseline in pre- and post-bronchodilator CO diffusion capacity at visit 10 (week 24) and at time of response
次要结局
- Mean change from baseline in fatique(52 weeks)
- Mean change from baseline in pre- and post-bronchodilator forced vital capacity (FVC) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Mean change from baseline in pre- and post-bronchodilator residual volume (RV) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Mean change from baseline in pre- and post-bronchodilator total lung capacity (TLC) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Mean change from baseline in pre- and post-bronchodilator airway resistance over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Mean change from baseline in pre- and post-bronchodilator inspiratory capacity (IC) over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Mean change from baseline in pre- and post-bronchodilator CO diffusion capacity over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 months)
- Exercise tolerance in a subgroup of patients: Mean change from baseline in inspiratory capacity (IC)(1, 3, 6, 9 and 12 month)
- Time to clinical response and time to change of baseline parameters of clinical Response: sence of smell(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: sense of taste(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: lung volume(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: CO Diffusion capacity(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: FEV1 reversibility(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: exhaled NO (eNO)(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: blood eosinophils(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: eosinophilic cationic Protein (ECP)(52 weeks)
- Time to clinical response and time to change of baseline parameters of clinical Response: blood periostin(52 weeks)
- Mean change from baseline in Asthma Control Questionnaire (ACQ)(52 weeks)
- Mean change from baseline in Asthma Quality of Life Questionnaire (AQLQ)(52 weeks)
- Mean change from baseline in St. George´s Respiratory Questionnaire (SQRG)(52 weeks)
- Mean change from baseline in Dyspnoe Index (BDI/TDI)(52 weeks)
- Exercise tolerance in a subgroup of patients: Mean change from baseline in exercise endurance time(1, 3, 6, 9 and 12 month)
- Exercise tolerance in a subgroup of patients: Mean change from baseline in exertional dyspnea and leg discomfort (Borg CR10 Scale®)(1, 3, 6, 9 and 12 month)
- Mean change from baseline in number of days off school/work over the 48-week treatment period(48 weeks)
- Time to first clinically significant exacerbation requiring oral or systemic corticosteroids, hospitalization, and/or emergency department (ED) visits(52 weeks)
- Frequency of clinically significant exacerbations(52 weeks)
- Time to first exacerbation requiring hospitalization or emergency department (ED) visit(52 weeks)
- Frequency of exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit (ICU)) or ED visits(52 weeks)
- GETE rating by physician and patient at time of response and over the 52-week treatment period at pre-specified timepoints (1, 3, 6, 9 and 12 months)(1, 3, 6, 9 and 12 month)
- Mean change in proportion of patients with nasal polyps, chronic sinusitis and loss of smell and taste(52 weeks)
- Clinical response to mepolizumab in relation to asthma parameters which potentially predict clinical response(52 weeks)
- Routine safety assessment (AE and SAE reporting, withdrawals, pregnancy, hematological and clinical chemistry parameters, ECG and vital signs (pulse rate and systolic and diastolic blood pressure))(52 weeks)
研究者
PD Dr. Stephanie Korn
principal investigator
Johannes Gutenberg University Mainz