search
Back to results

Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations (MATERIAL)

Primary Purpose

Asthma, Viral Infection

Status
Unknown status
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Mepolizumab
Placebo
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Asthma focused on measuring Asthma, Viral, Infection, Inflammation, Mepolizumab, Eosinophilia

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Academic Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Mepolizumab

Saline

Arm Description

Outcomes

Primary Outcome Measures

FEV1
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

Secondary Outcome Measures

Viral load
Viral load in nasal swab and bronchial brushes
Sputum eosinophils
Change in sputum eosinophils
Cell influx in bronchoalveolar lavage fluid
Influx of neutrophils, eosinophils, macrophages, monocytes, T en B lymphocytes into the lungs
Pro-inflammatory cytokines in bronchoalveolar lavage fluid
Measurement of IL-6, IL-8 and IFN-y in bronchoaveolar lavage fluid
Antibody production
Anti RV-16 antibodies are measured in serum

Full Information

First Posted
January 25, 2012
Last Updated
February 6, 2012
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
The Netherlands Asthma Foundation, GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT01520051
Brief Title
Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations
Acronym
MATERIAL
Official Title
The Efficacy of Mepolizumab Treatment on Rhinovirus Induced Asthma Exacerbations
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Unknown status
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
March 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
The Netherlands Asthma Foundation, GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Viral Infection
Keywords
Asthma, Viral, Infection, Inflammation, Mepolizumab, Eosinophilia

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mepolizumab
Arm Type
Experimental
Arm Title
Saline
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Mepolizumab
Other Intervention Name(s)
Mepolizumab, SB240563
Intervention Description
3 monthly intravenous infusions of 750 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
3 monthly intravenous infusions with saline
Primary Outcome Measure Information:
Title
FEV1
Description
Change in pre-bronchodilator FEV1 between day 70 and day 77, i.e. 1 day prior and 6 days after RV16 challenge.
Time Frame
1 day prior and 6 days after RV16 challenge
Title
Questionnaire to score asthma and common cold complaints
Time Frame
During 14 days following viral infection
Secondary Outcome Measure Information:
Title
Viral load
Description
Viral load in nasal swab and bronchial brushes
Time Frame
Day 6 after viral infection
Title
Sputum eosinophils
Description
Change in sputum eosinophils
Time Frame
Before and after mepolizumab infusion
Title
Cell influx in bronchoalveolar lavage fluid
Description
Influx of neutrophils, eosinophils, macrophages, monocytes, T en B lymphocytes into the lungs
Time Frame
6 days after viral infection
Title
Pro-inflammatory cytokines in bronchoalveolar lavage fluid
Description
Measurement of IL-6, IL-8 and IFN-y in bronchoaveolar lavage fluid
Time Frame
6 days after viral infection
Title
Antibody production
Description
Anti RV-16 antibodies are measured in serum
Time Frame
6 weeks after infection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne M Bal, PhD
Phone
+31 205668043
Email
s.m.bal@amc.uva.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Koenraad F van der Sluijs, PhD
Phone
+31 205668224
Email
kvandersluijs@amc.uva.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René Lutter, PhD
Organizational Affiliation
Academic Medical Center, Respiratory Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elisabeth H Bel, MD, PhD
Organizational Affiliation
Academic Medical Center, Respiratory Medicine
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Peter J Sterk, PhD
Organizational Affiliation
Academic Medical Center, Respiratory Medicine
Official's Role
Study Director
Facility Information:
Facility Name
Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
René Lutter, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
19264687
Citation
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.
Results Reference
background
PubMed Identifier
19264686
Citation
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.
Results Reference
background
PubMed Identifier
11191542
Citation
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.
Results Reference
background
PubMed Identifier
18768794
Citation
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.
Results Reference
background

Learn more about this trial

Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations

We'll reach out to this number within 24 hrs