Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations
Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations
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:

 1. Reduces virus-induced bronchial inflammation

 2. Attenuates virus-induced asthma symptoms, airflow limitation and bronchial
 hyperresponsiveness.

 3. Enhances cellular immune responses to the virus.

 The aims of this study are to:

 1. To investigate whether IL-5 neutralization reduces the inflammatory response to viral
 airway infections in allergic asthma patients

 2. To investigate whether IL-5 neutralization prevents or reduces asthma symptoms during
 virus-induced asthma exacerbations

 3. To investigate whether IL-5 neutralization affects the cellular immune response to viral
 airway infections in allergic asthma patients
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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)