Clinical trial NCT02660489: Effect of OC459 on the Response to Rhinovirus Challenge in Asthma
Official title: Effect of the CRTH2 Antagonist OC459 on the Response to Rhinovirus Challenge in Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Rhinovirus
Picornaviridae Infections
Common Cold
Keywords: CRTH2 antagonist
Prostaglandin D2 receptor
Anti-Asthmatic Agents
OC459
Allergic asthma
Eosinophilia
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: Atopix Therapeutics, Ltd.
First posted: 2016-01-21
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Lower Respiratory Symptom Score
timeFrame: During 14 days following rhinovirus inoculation
Secondary outcomes:
measure: Change in Asthma Control Questionnaire (ACQ)-6 Score
timeFrame: Baseline, 10 days post rhinovirus inoculation
measure: Percentage Change in Peak Expiratory Flow Rate
timeFrame: Baseline and up to 14 days post rhinovirus inoculation
measure: Change in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and up to 14 days post rhinovirus inoculation
measure: Change in Exhaled Nitric Oxide (FeNO)
timeFrame: Baseline and up to 10 days post rhinovirus inoculation
measure: Changes in Airway Hyper Responsiveness (Histamine)
timeFrame: Baseline and 7 days post rhinovirus inoculation
measure: Viral Load (in Nasal Lavage Samples)
timeFrame: Up to 14 days post rhinovirus inoculation
measure: Total Upper Respiratory Symptom Score
timeFrame: During 14 days following rhinovirus inoculation
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Mary's Hospital
state: Greater London
Study officials:
affiliation: National Heart & Lung Institute, Imperial College London
name: Sebastian L Johnston, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: