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Effect of OC459 on the Response to Rhinovirus Challenge in Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02660489
Recruitment Status : Completed
First Posted : January 21, 2016
Results First Posted : February 26, 2021
Last Update Posted : February 26, 2021
Sponsor:
Collaborators:
Medical Research Council
Atopix Therapeutics, Ltd.
Information provided by (Responsible Party):
Imperial College London

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.

Condition or disease Intervention/treatment Phase
Asthma Rhinovirus Picornaviridae Infections Common Cold Drug: OC459 Drug: Placebo Other: Rhinovirus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of the CRTH2 Antagonist OC459 on the Response to Rhinovirus Challenge in Asthma
Actual Study Start Date : January 2015
Actual Primary Completion Date : February 2018
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: OC459 (CRTH2 antagonist)
OC459 50mg once daily for 5 weeks
Drug: OC459
Other Name: OC000459

Other: Rhinovirus
Inoculation with rhinovirus serotype 16

Placebo Comparator: Placebo
Placebo tablet once daily for 5 weeks
Drug: Placebo
Other: Rhinovirus
Inoculation with rhinovirus serotype 16




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Change in Asthma Control Questionnaire (ACQ)-6 Score [ Time Frame: Baseline, 10 days post rhinovirus inoculation ]
    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.

  2. Percentage Change in Peak Expiratory Flow Rate [ Time Frame: Baseline and up to 14 days post rhinovirus inoculation ]
    Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)

  3. Change in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline and up to 14 days post rhinovirus inoculation ]
    Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)

  4. Change in Exhaled Nitric Oxide (FeNO) [ Time Frame: Baseline and up to 10 days post rhinovirus inoculation ]
    Percentage change from baseline (rhinovirus inoculation, day 0) to peak during infection (highest of measurements on days 3, 5, 7, 10 post inoculation)

  5. Changes in Airway Hyper Responsiveness (Histamine) [ Time Frame: Baseline and 7 days post rhinovirus inoculation ]
    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

  6. Viral Load (in Nasal Lavage Samples) [ Time Frame: Up to 14 days post rhinovirus inoculation ]
    Peak during infection (up to day 14)

  7. Total Upper Respiratory Symptom Score [ Time Frame: During 14 days following rhinovirus inoculation ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02660489


Locations
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United Kingdom
St Mary's Hospital
London, Greater London, United Kingdom, W2 1PG
Sponsors and Collaborators
Imperial College London
Medical Research Council
Atopix Therapeutics, Ltd.
Investigators
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Principal Investigator: Sebastian L Johnston, MBBS PhD National Heart & Lung Institute, Imperial College London
  Study Documents (Full-Text)

Documents provided by Imperial College London:
Study Protocol  [PDF] July 4, 2017
Statistical Analysis Plan  [PDF] March 13, 2018

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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT02660489    
Other Study ID Numbers: ORCA2015
First Posted: January 21, 2016    Key Record Dates
Results First Posted: February 26, 2021
Last Update Posted: February 26, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
CRTH2 antagonist
Prostaglandin D2 receptor
Anti-Asthmatic Agents
OC459
Allergic asthma
Eosinophilia
Additional relevant MeSH terms:
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Common Cold
Picornaviridae Infections
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiratory Tract Infections
Infections
RNA Virus Infections
Virus Diseases