Effect of OC459 on the response to rhinovirus challenge in asthma
Research type
Research Study
Full title
Effect of the CRTH2 antagonist OC459 on the response to rhinovirus challenge in asthma
IRAS ID
181049
Contact name
Sebastian Johnston
Contact email
Sponsor organisation
Imperial College
Eudract number
2015-002555-10
Duration of Study in the UK
2 years, 3 months, 1 days
Research summary
The aim of this study is to assess the effectiveness of the drug OC459 in preventing or attenuating the symptoms of an asthma exacerbation after rhinovirus infection.
Asthma is the most common chronic respiratory disease, and in many countries prevalence is rising. The major morbidity, mortality and health care costs related to asthma are a result of periods of acutely increased symptomatology called ‘exacerbations’. Most exacerbations are caused by rhinovirus, the virus associated with the common cold. There are few treatments to prevent and treat exacerbations, and despite these >50% of adult asthmatics reported having an exacerbation in the last year. There is therefore a major unmet need.
Experimentally infecting asthmatics with rhinovirus, a methodology that has been safely used for >15 years, induces an asthma exacerbation in ~85%. This model offers the possibility to investigate treatment effects on asthma exacerbations with a small number of subjects, minimising the numbers exposed to a novel drug with limited safety data. In contrast, trials of therapies powered to evaluate an effect on naturally occurring exacerbations require several hundred subjects, a long study period to capture enough events, and are significantly more expensive to carry out.
Using this model we have shown that several inflammatory molecules, including prostaglandin D2 (PGD2), are significantly increased during rhinovirus-induced asthma exacerbations, with the levels of PGD2 strongly correlating with the severity of the symptoms. Moreover other studies have shown that when PGD2 binds the CRTH2 receptor, it stimulates the release of a number of inflammatory molecules also associated with asthma exacerbations. Blocking the CRTH2 receptor therefore appears an extremely promising target with potential to limit the virus-induced inflammation underpinning many asthma exacerbations.
The proposed study is a double-blind, randomised trial comparing the CRTH2 antagonist OC459 to placebo. This is the gold standard design for a clinical trial.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
15/LO/1666
Date of REC Opinion
23 Oct 2015
REC opinion
Further Information Favourable Opinion