Mepolizumab Treatment for Rhinovirus-induced Asthma Exacerbations

NCT01520051 | Unknown Phase 3 DMC

• 1 other identifier: MATERIAL
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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. 1.Reduces virus-induced bronchial inflammation
2. 2.Attenuates virus-induced asthma symptoms, airflow limitation and bronchial hyperresponsiveness.
3. 3.Enhances cellular immune responses to the virus.
4. 4.To investigate whether IL-5 neutralization reduces the inflammatory response to viral airway infections in allergic asthma patients
5. 5.To investigate whether IL-5 neutralization prevents or reduces asthma symptoms during virus-induced asthma exacerbations
6. 6.To investigate whether IL-5 neutralization affects the cellular immune response to viral airway infections in allergic asthma patients

Conditions

Asthma; Viral Infection

Keywords

Asthma; Viral; Infection; Inflammation; Mepolizumab; Eosinophilia

Outcome Measures

Primary Outcomes (2)

• FEV1

  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

  During 14 days following viral infection

Secondary Outcomes (5)

• Viral load

  Day 6 after viral infection

• Sputum eosinophils

  Before and after mepolizumab infusion

• Cell influx in bronchoalveolar lavage fluid

  6 days after viral infection

• Pro-inflammatory cytokines in bronchoalveolar lavage fluid

  6 days after viral infection

• Antibody production

  6 weeks after infection

Study Arms (2)

Mepolizumab

EXPERIMENTAL

Drug: Mepolizumab

Saline

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Mepolizumab DRUG

3 monthly intravenous infusions of 750 mg

Also known as: Mepolizumab, SB240563

Mepolizumab

Placebo DRUG

3 monthly intravenous infusions with saline

Saline

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• The Netherlands Asthma Foundation: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

RECRUITING

Related Publications (4)

• 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.

  PMID: 19264687 BACKGROUND

• 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.

  PMID: 19264686 BACKGROUND

• 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.

  PMID: 11191542 BACKGROUND

• 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.

  PMID: 18768794 BACKGROUND

MeSH Terms

Conditions

Asthma; Virus Diseases; Infections; Inflammation; Eosinophilia

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• René Lutter, PhD

  Academic Medical Center, Respiratory Medicine

  PRINCIPAL INVESTIGATOR

• Elisabeth H Bel, MD, PhD

  Academic Medical Center, Respiratory Medicine

  STUDY DIRECTOR

• Peter J Sterk, PhD

  Academic Medical Center, Respiratory Medicine

  STUDY DIRECTOR

Central Study Contacts

Suzanne M Bal, PhD

CONTACT

+31 205668043; s.m.bal@amc.uva.nl

Koenraad F van der Sluijs, PhD

CONTACT

+31 205668224; kvandersluijs@amc.uva.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoc, investigator of the study

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: January 27, 2012
• Study Start: January 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: February 7, 2012

Record last verified: 2012-02

Locations

NL (1)