Effect of OC459 on the Response to Rhinovirus Challenge in Asthma
Effect of OC459 on the Response to Rhinovirus Challenge in Asthma
The aim of this study is to assess the effectiveness of a CRTH2 receptor antagonist, OC459,
 in preventing or attenuating the worsening of asthma symptoms during rhinovirus infection.
 The study is a double blind, randomised trial in which half the subjects will receive OC459
 and the other half placebo, before being inoculated with rhinovirus, that would normally
 induce a worsening of asthma symptoms i.e. an exacerbation.
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 inoculating patients with asthma with rhinovirus, a methodology that has been
 safely used for >15 years, induces an infection and worsening symptoms 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 the investigators 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.
Inclusion Criteria:

 -  Age 18--55 years

 -  Male or female

 -  Clinical diagnosis of asthma for at least 6 months prior to screening

 -  An Asthma Control Questionnaire (ACQ) Score >0.75

 -  Positive histamine challenge test (PC20 <8 µg/ml, or <12 µg/ml and bronchodilator
 response ≥ 12%)

 -  Worsening asthma symptoms with infection since last change in asthma therapy

 -  Positive skin prick test to common aeroallergens (e.g. animal epithelia, dust mite)

 -  Treatment comprising inhaled corticosteroids (ICS) or combination inhaler (Long
 -Acting Beta Agonist with ICS), with a daily ICS dose of at least 100mcg fluticasone
 or equivalent.

 -  Participant is willing for their GP to be informed of their participation.

 -  English speaker

 Exclusion Criteria:

 -  Presence of clinically significant diseases other than asthma, which, in the opinion
 of the investigator, may either put the patient at risk because of participation in
 the trial, or diseases which may influence the results of the study or the patient's
 ability to take part in it

 -  Smoking history over past 12 months

 -  Seasonal allergic rhinitis symptoms at screening

 -  Asthma exacerbation or viral illness within the previous 6 weeks

 -  Current or concomitant use of oral steroids, anti--leukotrienes or monoclonal
 antibodies

 -  Pregnant or breast-feeding women (patients should not be enrolled if they plan to
 become pregnant during the time of study participation)

 -  Contact with infants <6 months or immunocompromised persons, elderly and infirm at
 home or at work

 -  Subjects who have known evidence of lack of adherence to medications and/or ability to
 follow physician's recommendations