Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations

NCT ID: NCT01520051

Last Updated: 2012-02-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2014-03-31

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:

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

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.

Conditions

Asthma; Viral Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Mepolizumab

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: DRUG

3 monthly intravenous infusions of 750 mg

Saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

3 monthly intravenous infusions with saline

Interventions

Mepolizumab

3 monthly intravenous infusions of 750 mg

Intervention Type: DRUG

Placebo

3 monthly intravenous infusions with saline

Intervention Type: DRUG

Other Intervention Names

Mepolizumab, SB240563

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Asthma Foundation

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Bal

Postdoc, investigator of the study

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

René Lutter, PhD

Role: PRINCIPAL_INVESTIGATOR

Academic Medical Center, Respiratory Medicine

Elisabeth H Bel, MD, PhD

Role: STUDY_DIRECTOR

Academic Medical Center, Respiratory Medicine

Peter J Sterk, PhD

Role: STUDY_DIRECTOR

Academic Medical Center, Respiratory Medicine

Locations

Academic Medical Center

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Suzanne M Bal, PhD

Role: CONTACT

s.m.bal@amc.uva.nl

+31 205668043

Koenraad F van der Sluijs, PhD

Role: CONTACT

kvandersluijs@amc.uva.nl

+31 205668224

References

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.

Reference Type: BACKGROUND

PMID: 19264687 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19264686 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11191542 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18768794 (View on PubMed)

Other Identifiers

MATERIAL

Identifier Type: -

Identifier Source: org_study_id