Asthma MedDRA version: 20.0 Level: LLT Classification code 10001705 Term: Allergic asthma System Organ Class: 100000015470 MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level:
Conditions
Interventions
Product Name: OC459
Product Code: OC000459
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OC000459
Current Sponsor code: O
Sponsors
Imperial College
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Presence of clinically significant diseases other than asthma (cardiovascular, renal, hepatic, gastrointestinal, haematological, pulmonary, neurological, genitourinary, autoimmune, endocrine, metabolic, neoplasia etc.), 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 or during the 3 week run-in (prior to rhinovirus inoculation). • Asthma exacerbation or viral illness within the previous 6 weeks or during the 3 week run-in (prior to rhinovirus inoculation). • 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 (see note regarding contraception below). • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall aim of this study is to assess the effectiveness of the study drug (OC459) in preventing or attenuating the worsening of asthma symptoms (an asthma exacerbation) that occurs when asthma sufferers catch a cold (defined as an infection with the virus rhinovirus). The study drug will be compared with a placebo to find out the extent of any improvement in the condition of the participants. A placebo is a medically noneffective copy of the drug being tested; it looks and tastes the same as the treatment drug (it can be seen as a dummy drug). In healthy subjects, rhinovirus infection causes symptoms of a cold e.g. sneezing, runny nose. In patients with asthma, rhinovirus infection causes a worsening of their asthma symptoms (e.g. breathlessness, wheeze) because of the way the immune system reacts to the virus. The study drug OC459 blocks activation of receptor cells found in the immune system and by blocking that activation may prevent an exacerbation of symptoms. Changes in as ; Secondary Objective: Our secondary objectives are to: 1) Determine the influence of the study drug OC459 on other clinical and laboratory parameters during rhinovirus infection: • Health status, as assessed by validated questionnaires • Lung function, measured both using a home spirometer which we will provide and on subject visits • Exhaled nitric oxide (FeNO) levels in the breath, which are a marker of inflamed airways • Airway hyperresponsiveness, measured in a histamine challenge test, a routine test that quantifies the degree of airway narrowing in patients with asthma • Viral load, i.e. the number of copies of rhinovirus in nasal and bronchoscopic samples 2) Determine the mechanism of action of the study drug OC459, by assessing its impact on inflammatory cell numbers and inflammatory mediato | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Difference between OC459 and placebo groups in the following (all measured as peak and change from baseline): • Increase in ACQ score (health status) • Reduction in Forced Expiratory Volume in 1 second (FEV1) or Peak Expiratory Flow (PEF) on spirometry • Increase in FeNO • Decrease in PC20 • Virus load in nasal lavage – total (area under the curve) for days 2-5+7+10, as well as peak and difference from baseline • Increase in sputum eosinophilia • Leukocyte numbers (e.g. ILC2, Th2) in FACS-sorted BAL, serum and nasal scrapes, and in immunohistochemistry-stained biopsies • Cytokine levels (e.g. IL-4, IL-5, IL-13) in nasosorption, nasal lavage, bronchosorption, BAL • mRNA expression of same cytokines in cells in BAL and bronchial biopsies • In ex vivo studies, protein and mRNA levels of antiviral cytokines (e.g. IFN-a, IFN-?) produced by cells from blood, BAL, and bronchial brushings in response to rhinovirus infection • Difference in number of adverse events in OC459 and placebo groups ; Timepoint(s) of evaluation of this end point: All secondary endpoints will be assessed prior to (days -8 and -7), during, and at the end of rhinovirus infection (days 0 to 14). Some endpoints (e.g. leukocyte numbers) will additionally be assessed at the first baseline visit, prior to the first dose of the study drug, to assess the effect of the drug. In addition health status and lung function will be assessed by participants at home, and once more by investigators, 6 weeks after rhinovirus inoculation (day 42). | — |
Countries
United Kingdom
Contacts
Public ContactDr Hugo Farne
Imperial College
Outcome results
None listed