Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations (MATERIAL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was  Recruiting
Sponsor:
Collaborators:
The Netherlands Asthma Foundation
GlaxoSmithKline
Information provided by (Responsible Party):
Suzanne Bal, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01520051
First received: January 25, 2012
Last updated: February 6, 2012
Last verified: February 2012
  Purpose

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

Condition Intervention Phase
Asthma
Viral Infection
Drug: Mepolizumab
Drug: Placebo
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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


Estimated Enrollment: 48
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)
Arms Assigned Interventions
Experimental: Mepolizumab Drug: Mepolizumab
3 monthly intravenous infusions of 750 mg
Other Name: Mepolizumab, SB240563
Placebo Comparator: Saline Drug: Placebo
3 monthly intravenous infusions with saline

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01520051

Contacts
Contact: Suzanne M Bal, PhD +31 205668043 s.m.bal@amc.uva.nl
Contact: Koenraad F van der Sluijs, PhD +31 205668224 kvandersluijs@amc.uva.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1105 AZ
Principal Investigator: René Lutter, PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
The Netherlands Asthma Foundation
GlaxoSmithKline
Investigators
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
  More Information

Publications:
Responsible Party: Suzanne Bal, Postdoc, investigator of the study, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01520051     History of Changes
Other Study ID Numbers: MATERIAL
Study First Received: January 25, 2012
Last Updated: February 6, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Asthma
Viral
Infection
Inflammation
Mepolizumab
Eosinophilia

Additional relevant MeSH terms:
Asthma
Virus Diseases
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014