- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01520051
Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations (MATERIAL)
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
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Studietype
Registrering (Forventet)
Fase
- Fase 3
Kontakter og plasseringer
Studiesteder
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-
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Amsterdam, Nederland, 1105 AZ
- Rekruttering
- Academic Medical Center
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Hovedetterforsker:
- René Lutter, PhD
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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)
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Placebo komparator: Saltvann
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3 monthly intravenous infusions with saline
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Eksperimentell: Mepolizumab
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3 monthly intravenous infusions of 750 mg
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
FEV1
Tidsramme: 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
Tidsramme: During 14 days following viral infection
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During 14 days following viral infection
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Viral load
Tidsramme: Day 6 after viral infection
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Viral load in nasal swab and bronchial brushes
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Day 6 after viral infection
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Sputum eosinophils
Tidsramme: Before and after mepolizumab infusion
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Change in sputum eosinophils
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Before and after mepolizumab infusion
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Cell influx in bronchoalveolar lavage fluid
Tidsramme: 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
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Pro-inflammatory cytokines in bronchoalveolar lavage fluid
Tidsramme: 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
Tidsramme: 6 weeks after infection
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Anti RV-16 antibodies are measured in serum
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6 weeks after infection
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Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: René Lutter, PhD, Academic Medical Center, Respiratory Medicine
- Studieleder: Elisabeth H Bel, MD, PhD, Academic Medical Center, Respiratory Medicine
- Studieleder: Peter J Sterk, PhD, Academic Medical Center, Respiratory Medicine
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- MATERIAL
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