Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations (MATERIAL)
6 février 2012 mis à jour par: Suzanne Bal, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
The Efficacy of Mepolizumab Treatment on 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:
- 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
Aperçu de l'étude
Statut
Inconnue
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Anticipé)
48
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
-
-
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Amsterdam, Pays-Bas, 1105 AZ
- Recrutement
- Academic Medical Center
-
Chercheur principal:
- René Lutter, PhD
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-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 50 ans (Adulte)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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)
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur placebo: Saline
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3 monthly intravenous infusions with saline
|
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Expérimental: Mepolizumab
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3 monthly intravenous infusions of 750 mg
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
FEV1
Délai: 1 day prior and 6 days after RV16 challenge
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Change in pre-bronchodilator FEV1 between day 70 and day 77, i.e. 1 day prior and 6 days after RV16 challenge.
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1 day prior and 6 days after RV16 challenge
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Questionnaire to score asthma and common cold complaints
Délai: During 14 days following viral infection
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During 14 days following viral infection
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Viral load
Délai: Day 6 after viral infection
|
Viral load in nasal swab and bronchial brushes
|
Day 6 after viral infection
|
|
Sputum eosinophils
Délai: Before and after mepolizumab infusion
|
Change in sputum eosinophils
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Before and after mepolizumab infusion
|
|
Cell influx in bronchoalveolar lavage fluid
Délai: 6 days after viral infection
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Influx of neutrophils, eosinophils, macrophages, monocytes, T en B lymphocytes into the lungs
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6 days after viral infection
|
|
Pro-inflammatory cytokines in bronchoalveolar lavage fluid
Délai: 6 days after viral infection
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Measurement of IL-6, IL-8 and IFN-y in bronchoaveolar lavage fluid
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6 days after viral infection
|
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Antibody production
Délai: 6 weeks after infection
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Anti RV-16 antibodies are measured in serum
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6 weeks after infection
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Les enquêteurs
- Chercheur principal: René Lutter, PhD, Academic Medical Center, Respiratory Medicine
- Directeur d'études: Elisabeth H Bel, MD, PhD, Academic Medical Center, Respiratory Medicine
- Directeur d'études: Peter J Sterk, PhD, Academic Medical Center, Respiratory Medicine
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009 Mar 5;360(10):973-84. doi: 10.1056/NEJMoa0808991. Erratum In: N Engl J Med. 2011 Feb 10;364(6):588.
- Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009 Mar 5;360(10):985-93. doi: 10.1056/NEJMoa0805435.
- Leckie MJ, ten Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000 Dec 23-30;356(9248):2144-8. doi: 10.1016/s0140-6736(00)03496-6.
- Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SL. Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13562-7. doi: 10.1073/pnas.0804181105. Epub 2008 Sep 3.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 janvier 2012
Achèvement primaire (Anticipé)
1 décembre 2013
Achèvement de l'étude (Anticipé)
1 mars 2014
Dates d'inscription aux études
Première soumission
25 janvier 2012
Première soumission répondant aux critères de contrôle qualité
25 janvier 2012
Première publication (Estimation)
27 janvier 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
7 février 2012
Dernière mise à jour soumise répondant aux critères de contrôle qualité
6 février 2012
Dernière vérification
1 février 2012
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- MATERIAL
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