Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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:

  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

Studieoversigt

Status

Ukendt

Betingelser

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

48

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

      • Amsterdam, Holland, 1105 AZ
        • Rekruttering
        • Academic Medical Center
        • Ledende efterforsker:
          • René Lutter, PhD

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 50 år (Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Tredobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Placebo komparator: Saltvand
3 monthly intravenous infusions with saline
Eksperimentel: Mepolizumab
3 monthly intravenous infusions of 750 mg
Andre navne:
  • Mepolizumab, SB240563

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
FEV1
Tidsramme: 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.
1 day prior and 6 days after RV16 challenge
Questionnaire to score asthma and common cold complaints
Tidsramme: During 14 days following viral infection
During 14 days following viral infection

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Viral load
Tidsramme: Day 6 after viral infection
Viral load in nasal swab and bronchial brushes
Day 6 after viral infection
Sputum eosinophils
Tidsramme: Before and after mepolizumab infusion
Change in sputum eosinophils
Before and after mepolizumab infusion
Cell influx in bronchoalveolar lavage fluid
Tidsramme: 6 days after viral infection
Influx of neutrophils, eosinophils, macrophages, monocytes, T en B lymphocytes into the lungs
6 days after viral infection
Pro-inflammatory cytokines in bronchoalveolar lavage fluid
Tidsramme: 6 days after viral infection
Measurement of IL-6, IL-8 and IFN-y in bronchoaveolar lavage fluid
6 days after viral infection
Antibody production
Tidsramme: 6 weeks after infection
Anti RV-16 antibodies are measured in serum
6 weeks after infection

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Ledende efterforsker: 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

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. januar 2012

Primær færdiggørelse (Forventet)

1. december 2013

Studieafslutning (Forventet)

1. marts 2014

Datoer for studieregistrering

Først indsendt

25. januar 2012

Først indsendt, der opfyldte QC-kriterier

25. januar 2012

Først opslået (Skøn)

27. januar 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

7. februar 2012

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. februar 2012

Sidst verificeret

1. februar 2012

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Mepolizumab

Abonner