AsthmaPhase 2NCT02660489
Effect of OC459 on the Response to Rhinovirus Challenge in Asthma
A Phase 2 study testing OC459 and Rhinovirus in people with Asthma and Rhinovirus, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Asthma, Rhinovirus, Picornaviridae Infections
- What is being tested?
- OC459 and Rhinovirus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2015to Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of the CRTH2 Antagonist 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.
Read the 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
- Being tested
- OC459, Placebo, Rhinovirus
- Keywords
- CRTH2 antagonist, Prostaglandin D2 receptor, Anti-Asthmatic Agents, OC459, Allergic asthma, Eosinophilia
- Medical subject headings
- Asthma, Picornaviridae Infections, Common Cold, Eosinophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OC459Drug
Also called OC000459
PlaceboDrug
RhinovirusOther
Inoculation with rhinovirus serotype 16
| Study group | Role | What they receive |
|---|---|---|
| OC459 (CRTH2 antagonist) | Experimental | OC459 50mg once daily for 5 weeks Receives: Drug: OC459; Other: Rhinovirus |
| Placebo | Placebo comparator | Placebo tablet once daily for 5 weeks Receives: Drug: Placebo; Other: Rhinovirus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Lower Respiratory Symptom Score
Sum of daily scores for 14 days. Seven symptoms (cough on waking, wheeze on waking, daytime cough, daytime wheeze, daytime chest tightness, daytime breathlessness, nocturnal cough/wheeze/breathlessness) ranked from 0 (none) to 3 (severe). Range 0 to 294; higher is more symptomatic.
Measured: During 14 days following rhinovirus inoculation
Secondary outcomes (7)
Change in Asthma Control Questionnaire (ACQ)-6 Score
Change from baseline (rhinovirus inoculation, day 0) to day 10. The ACQ was developed to measure the adequacy of asthma control in clinical research and in clinical practice. The ACQ-6 asks subjects to grade their asthma control, assessed through six questions, over the previous seven days. Each question is rated on a seven-point scale ranging from 0 (well controlled) to six (extremely poorly controlled). The ACQ-6 score is the mean of the scores on the 6 items. Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.
Measured: Baseline, 10 days post rhinovirus inoculation
Percentage Change in Peak Expiratory Flow Rate
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
Measured: Baseline and up to 14 days post rhinovirus inoculation
Change in Forced Expiratory Volume in 1 Second (FEV1)
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
Measured: Baseline and up to 14 days post rhinovirus inoculation
Change in Exhaled Nitric Oxide (FeNO)
Percentage change from baseline (rhinovirus inoculation, day 0) to peak during infection (highest of measurements on days 3, 5, 7, 10 post inoculation)
Measured: Baseline and up to 10 days post rhinovirus inoculation
Changes in Airway Hyper Responsiveness (Histamine)
Assessed as the provocation concentration of histamine producing a 20% fall in FEV1, or PC20 Change from baseline (rhinovirus inoculation, day 0) to day 7
Measured: Baseline and 7 days post rhinovirus inoculation
Viral Load (in Nasal Lavage Samples)
Peak during infection (up to day 14)
Measured: Up to 14 days post rhinovirus inoculation
Total Upper Respiratory Symptom Score
Sum of daily scores for 14 days. Eight upper respiratory symptoms (sneezing; runny nose; blocked or stuffy nose; sore throat or hoarse voice; headache or face pain; generally unwell; chill, fever or shivery; cough) ranked from 0 (none) to 3 (severe). Range 0 to 336; higher is more symptomatic.
Measured: During 14 days following rhinovirus inoculation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2016 (estimated)
- Study startJan 2015
- Primary completionFeb 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, Atopix Therapeutics, Ltd.
- Responsible party
- Sponsor
- Investigators
- Sebastian L Johnston, MBBS PhD, Principal investigator, National Heart & Lung Institute, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02660489
- Sponsor's protocol ID
- ORCA2015
- Status last verified
- Feb 2021
- First submitted
- 12 Jan 2016
- Last updated
- 26 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the CRTH2 Antagonist OC459 on the Response to Rhinovirus Challenge in Asthma
- ClinicalTrials.gov ID
- NCT02660489
- Acronym / sponsor ID
- ORCA2015
- Conditions
- Asthma, Rhinovirus, Picornaviridae Infections, Common Cold
- Keywords
- CRTH2 antagonist, Prostaglandin D2 receptor, Anti-Asthmatic Agents, OC459, Allergic asthma, Eosinophilia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Medical Research Council, Atopix Therapeutics, Ltd.
- Study start
- Jan 2015 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 21 Jan 2016 (estimated)
- Results
- Posted 26 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OC459 (CRTH2 antagonist) | Experimental | Drug: OC459, Other: RhinovirusOC459 50mg once daily for 5 weeks |
| Placebo | Placebo comparator | Drug: Placebo, Other: RhinovirusPlacebo tablet once daily for 5 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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%)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OC459Also: OC000459 | Drug | OC459 (CRTH2 antagonist) |
| Placebo | Drug | Placebo |
| RhinovirusInoculation with rhinovirus serotype 16 | Other | OC459 (CRTH2 antagonist), Placebo |
Primary outcome
Total Lower Respiratory Symptom Score
Time frame: During 14 days following rhinovirus inoculation
Sum of daily scores for 14 days. Seven symptoms (cough on waking, wheeze on waking, daytime cough, daytime wheeze, daytime chest tightness, daytime breathlessness, nocturnal cough/wheeze/breathlessness) ranked from 0 (none) to 3 (severe). Range 0 to 294; higher is more symptomatic.
7 secondary outcomes
Change in Asthma Control Questionnaire (ACQ)-6 Score
Time frame: Baseline, 10 days post rhinovirus inoculation
Percentage Change in Peak Expiratory Flow Rate
Time frame: Baseline and up to 14 days post rhinovirus inoculation
Change in Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline and up to 14 days post rhinovirus inoculation
Change in Exhaled Nitric Oxide (FeNO)
Time frame: Baseline and up to 10 days post rhinovirus inoculation
Changes in Airway Hyper Responsiveness (Histamine)
Time frame: Baseline and 7 days post rhinovirus inoculation
Viral Load (in Nasal Lavage Samples)
Time frame: Up to 14 days post rhinovirus inoculation
Total Upper Respiratory Symptom Score
Time frame: During 14 days following rhinovirus inoculation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sebastian L Johnston, MBBS PhD principal investigator
National Heart & Lung Institute, Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OC459 and Rhinovirus in people with Asthma and Rhinovirus, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Lower Respiratory Symptom Score (time frame: During 14 days following rhinovirus inoculation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2021.