Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations (MATERIAL)
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
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||The Efficacy of Mepolizumab Treatment on Rhinovirus Induced Asthma Exacerbations|
- FEV1 [ Time Frame: 1 day prior and 6 days after RV16 challenge ] [ Designated as safety issue: No ]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 [ Time Frame: During 14 days following viral infection ] [ Designated as safety issue: No ]
- Viral load [ Time Frame: Day 6 after viral infection ] [ Designated as safety issue: No ]Viral load in nasal swab and bronchial brushes
- Sputum eosinophils [ Time Frame: Before and after mepolizumab infusion ] [ Designated as safety issue: No ]Change in sputum eosinophils
- Cell influx in bronchoalveolar lavage fluid [ Time Frame: 6 days after viral infection ] [ Designated as safety issue: No ]Influx of neutrophils, eosinophils, macrophages, monocytes, T en B lymphocytes into the lungs
- Pro-inflammatory cytokines in bronchoalveolar lavage fluid [ Time Frame: 6 days after viral infection ] [ Designated as safety issue: No ]Measurement of IL-6, IL-8 and IFN-y in bronchoaveolar lavage fluid
- Antibody production [ Time Frame: 6 weeks after infection ] [ Designated as safety issue: No ]Anti RV-16 antibodies are measured in serum
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
3 monthly intravenous infusions of 750 mg
Other Name: Mepolizumab, SB240563
|Placebo Comparator: Saline||
3 monthly intravenous infusions with saline
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.
|Contact: Suzanne M Bal, PhD||+31 email@example.com|
|Contact: Koenraad F van der Sluijs, PhD||+31 firstname.lastname@example.org|
|Academic Medical Center||Recruiting|
|Amsterdam, Netherlands, 1105 AZ|
|Principal Investigator: René Lutter, PhD|
|Principal Investigator:||René Lutter, PhD||Academic Medical Center, Respiratory Medicine|
|Study Director:||Elisabeth H Bel, MD, PhD||Academic Medical Center, Respiratory Medicine|
|Study Director:||Peter J Sterk, PhD||Academic Medical Center, Respiratory Medicine|