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Effect of OC459 on the Response to Rhinovirus Challenge in Asthma

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ClinicalTrials.gov Identifier: NCT02660489
Recruitment Status : Unknown
Verified August 2016 by Imperial College London.
Recruitment status was:  Recruiting
First Posted : January 21, 2016
Last Update Posted : August 18, 2017
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 symptoms of an asthma exacerbation after 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 infecting asthmatics with rhinovirus, a methodology that has been safely used for >15 years, induces an asthma exacerbation 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)
Estimated Enrollment : 28 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
Study Start Date : October 2015
Estimated Primary Completion Date : February 2018
Estimated 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 Tract Symptoms score [ Time Frame: During 14 days following rhinovirus inoculation ]
    Sum of daily scores for 14 days


Secondary Outcome Measures :
  1. Asthma Control Questionnaire (ACQ) score [ Time Frame: Assessed at baseline (day -21), day -8, day 0 (rhinovirus challenge), day 10, day 42 ]
  2. Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: During 14 days following rhinovirus inoculation (measured twice daily at home) ]
  3. Exhaled nitric oxide (FeNO) [ Time Frame: Measured at baseline (day -21), day -8, day 0 (rhinovirus challenge), day 3, 5, 7, 10, 42 ]
  4. Airway hyperresponsiveness (assessed as the provocation concentration of histamine producing a 20% fall in FEV1, or PC20) [ Time Frame: Assessed at baseline (day -21), day -8, day 7 ]
  5. Viral load (in sputum and nasal samples) [ Time Frame: Samples taken at baseline (day -21), day 0 (immediately before rhinovirus challenge), day 2, 3, 4, 5, 7, 10 ]
  6. Sputum eosinophilia [ Time Frame: Samples taken at baseline (day -21), day 0 (rhinovirus challenge), day 4, day 7 ]
  7. Leukocyte numbers (e.g. ILC2, Th2) in bronchoalveolar lavage (BAL) [ Time Frame: BAL samples taken 1 week pre- and day 5 post-rhinovirus challenge ]
  8. Cytokine levels (e.g. IL-4, IL-5, IL-13) in nasal and bronchial samples (on Synthetic Absorptive Matrix and in lavage samples) [ Time Frame: Samples taken at baseline (day -21), day 0 (immediately before rhinovirus challenge), day 2, 3, 4, 5, 7, 10 ]
  9. Adverse events [ Time Frame: Throughout study (9 weeks total, 3 weeks run-in period on drug/placebo, 2 weeks post-rhinovirus inoculation, 6 weeks after stopping drug/placebo) ]


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


Contacts
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Contact: Hugo Farne, BMBCh MA 07590250487 asthma.trial@imperial.ac.uk
Contact: Maria-Belén Trujillo-Torralbo, BSc 07590250487 asthma.trial@imperial.ac.uk

Locations
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United Kingdom
St Mary's Hospital Recruiting
London, Greater London, United Kingdom, W2 1PG
Contact: Hugo Farne, BMBCh MA    07590 250487    asthma.trial@imperial.ac.uk   
Contact: Maria-Belén Trujillo-Torralbo, BSc    07590 250487    asthma.trial@imperial.ac.uk   
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
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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
Last Update Posted: August 18, 2017
Last Verified: August 2016
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
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections