Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
125770
Study information
Scientific title
Acronym
Study hypothesis
Mepolizumab which is a monoclonal antibody against interleukin 5, will effectively suppress eosinophilic airway inflammation and lower exacerbation frequency in severe asthmatics with evidence of persistent eosinophilic airway inflammation and a history of recurrent asthma exacerbations (greater than or equal to 2/year).
The hypothesis is based upon previous studies that have demonstrated a temporal relationship between a rise in sputum eosinophilia predicting onset of exacerbations. Steroid therapy targeted at lowering sputum eosinophil counts have been effective in lowering exacerbation frequency. Following on from this, mepolizumab has been shown in pilot studies to be effective in lowering both blood and sputum eosinophil counts and if the previous observations are robust in their hypothesis that sputum eosinophilia is causally related to asthma exacerbations, then we would expect mepoloizumab to achieve control of exacerbations through its mechanism of action. The present study has been designed to test this hypothesis.
Ethics approval
Obtained before recruitment of the first participant.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Asthma
Intervention
12 month randomised double blind placebo contolled parallel group trial to receive either placebo or monoclonal antibody therapy to interleukin 5 (mepolizumab) - 750 mg intravenously over 30 minutes, monthly.
Intervention type
Drug
Phase
Not Applicable
Drug names
Mepolizumab
Primary outcome measure
Sputum eosinophil counts measured every 3 months and exacerbation frequency over the 12 month treatment period. We have 80% power to detect a 50% change in exacerbation frequency over 1 year for a total of 60 trial participants.
Secondary outcome measures
1. Asthma symptoms and quality of life
2. Computed tomography (CT) and bronchial biopsy evidence of airway remodelling (i.e. structural changes to the airway wall from long standing chronic airway inflammation)
Overall trial start date
01/08/2005
Overall trial end date
31/07/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 60 participants meeting American thoracic criteria for refractory asthma
2. On intensive corticosteroid therapy - either oral and/or inhaled
3. A history of two or more exacerbations of asthma requiring oral corticosteroid rescue therapy in one year
4. Evidence of persistent eosinophilic inflammation in sputum - sputum eosinophils greater than 3% of total cell count
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
60
Participant exclusion criteria
1. Participants who do not meet American Thoracic Society criteria for severe asthma
2. Participants who have not demonstrated evidence of persistent eosinophilic airway inflammation (sputum eosinophil counts of greater than or equal to 3% of total cell count
3. Partcipants who are current smokers or who have a cumulative smoking history of greater than 15 pack years
4. Participants with significant co morbidity - including other symptomatic respiratory diagnoses, evidence of recurrent bacterial respiratory tract infections (greater than or equal to 2 per year), symptomatic ischaemic heart disease and mental health or other conditions that interfere with participant compliance with the study
5. Pregnant females or women of child bearing age not practising effective contraception during the study
Recruitment start date
01/08/2005
Recruitment end date
31/07/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
University Hospitals of Leicester NHS Trust (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Added as of 02/01/2008:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
GlaxoSmithKline (UK)
Alternative name(s)
GlaxoSmithKline plc., GSK
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19264686
Publication citations
-
Results
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, 360, 10, 973-984, doi: 10.1056/NEJMoa0808991.