Effect of OC459 on the Response to Rhinovirus Challenge in Asthma

NCT ID: NCT02660489

Last Updated: 2021-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-02-28

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.

Conditions

Asthma; Rhinovirus; Picornaviridae Infections; Common Cold

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

OC459 (CRTH2 antagonist)

OC459 50mg once daily for 5 weeks

Group Type: EXPERIMENTAL

OC459

Intervention Type: DRUG

Rhinovirus

Intervention Type: OTHER

Inoculation with rhinovirus serotype 16

Placebo

Placebo tablet once daily for 5 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Rhinovirus

Intervention Type: OTHER

Inoculation with rhinovirus serotype 16

Interventions

OC459

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Rhinovirus

Inoculation with rhinovirus serotype 16

Intervention Type: OTHER

Other Intervention Names

OC000459

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

Atopix Therapeutics, Ltd.

INDUSTRY

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sebastian L Johnston, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

National Heart & Lung Institute, Imperial College London

Locations

St Mary's Hospital

London, Greater London, United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ORCA2015

Identifier Type: -

Identifier Source: org_study_id