The Efficacy of Mepolizumab Treatment on Rhinovirus Induced Asthma Exacerbations
试验速览
- 阶段
- 3 期
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- FEV1
研究概览
简要总结
Asthma is a chronic inflammatory disorder of the airways characterized by lower respiratory tract (LRT) symptoms such as wheeze, cough and airway obstruction. Patients with asthma frequently suffer from exacerbations, which can be triggered by allergens and, in particular, viral respiratory infections. It has recently been shown that mepolizumab, a humanized monoclonal antibody that neutralizes interleukin(IL)-5, markedly reduces the exacerbation rate in asthma patients with eosinophilic airway inflammation. Previous studies have indicated that in a mixed population (eosinophilic and non eosinophilic) of mild asthma patients, mepolizumab did not have an impact on lung function and asthma symptom scores upon allergen provocation, although it did on markers such as sputum and blood eosinophils. Together, these observations led to the hypothesis that mepolizumab treatment reduces the exacerbation rate by limiting virus-induced asthma exacerbations.
The investigators hypothesize that neutralization of IL-5 during virus infection in patients with allergic asthma:
- Reduces virus-induced bronchial inflammation
- Attenuates virus-induced asthma symptoms, airflow limitation and bronchial hyperresponsiveness.
- Enhances cellular immune responses to the virus.
The aims of this study are to:
- To investigate whether IL-5 neutralization reduces the inflammatory response to viral airway infections in allergic asthma patients
- To investigate whether IL-5 neutralization prevents or reduces asthma symptoms during virus-induced asthma exacerbations
- To investigate whether IL-5 neutralization affects the cellular immune response to viral airway infections in allergic asthma patients
详细描述
Mild allergic asthma subjects receive three times an infusion containing 750 mg of mepolizumab. Two weeks after the third infusion, subjects will be experimentally infected with RV16. One day before and six days after infection a bronchoscopy will be performed to collect bronchoalveolar lavage fluid and bronchial brushes. Blood will be collected at each infusion and each bronchoscopy and at least 6 weeks after infection. Lung function will be evaluated throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 - 50 years
- •History of episodic chest tightness and wheezing
- •Intermittent or mild persistent asthma according to the criteria by the Global Initiative for Asthma
- •Non-smoking or stopped smoking more than 12 months ago and ≤ 5 pack years (PY)
- •Clinically stable, no history of exacerbations within the last 6 weeks prior to the study
- •Steroid-naïve or those patients who are currently not on corticosteroids and have not taken any corticosteroids by any dosing-routes within 2 weeks prior to the study. Occasional usage of inhaled short-acting beta2-agonists as rescue medication is allowed, prior and during the study
- •Baseline FEV1 > 80% of predicted
- •Airway hyperresponsiveness, indicated by a positive acetyl-ß-methylcholine bromide (MeBr) challenge with PC20 < 9.8 mg/ml
- •Positive skin prick test (SPT) to one or more of the 12 common aeroallergen extracts, defined as a wheal with an average diameter of > 3mm
- •No other clinically significant abnormality on medical history and clinical examination
排除标准
- •Presence of antibodies directed against RV16 in serum (titer > 4), measured at visit 1
- •History of clinical significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness
- •Women who are pregnant, lactating or who have a positive urine pregnancy test at visit 1
- •Chronic use of any other medication for treatment of lung disease other than short-acting beta2-agonists
- •Participation in any clinical investigational drug treatment protocol within the preceding 3 months
- •Ongoing use of tobacco products of any kind or previous usage with ≥ 6 total PY
- •Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the patient
- •People with young children (< 2 years)
研究组 & 干预措施
Mepolizumab
干预措施: Mepolizumab (Drug)
Saline
干预措施: Placebo (Drug)
结局指标
主要结局
FEV1
时间窗: 1 day prior and 6 days after RV16 challenge
Change in pre-bronchodilator FEV1 between day 70 and day 77, i.e. 1 day prior and 6 days after RV16 challenge.
Questionnaire to score asthma and common cold complaints
时间窗: During 14 days following viral infection
次要结局
- Viral load(Day 6 after viral infection)
- Sputum eosinophils(Before and after mepolizumab infusion)
- Cell influx in bronchoalveolar lavage fluid(6 days after viral infection)
- Pro-inflammatory cytokines in bronchoalveolar lavage fluid(6 days after viral infection)
- Antibody production(6 weeks after infection)
研究者
Suzanne Bal
Postdoc, investigator of the study
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)