Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Ian Pavord

ORCID ID

Contact details

Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom

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 measures

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

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

http://www.uhl-tr.nhs.uk/

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)

GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

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

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19264686

Publication citations

  1. 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.

Editorial Notes