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Effect of OC459 on the Response to Rhinovirus Challenge in Asthma

Primary Purpose

Asthma, Rhinovirus, Picornaviridae Infections

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
OC459
Placebo
Rhinovirus
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring CRTH2 antagonist, Prostaglandin D2 receptor, Anti-Asthmatic Agents, OC459, Allergic asthma, Eosinophilia

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St Mary's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

OC459 (CRTH2 antagonist)

Placebo

Arm Description

OC459 50mg once daily for 5 weeks

Placebo tablet once daily for 5 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Percentage Change in Peak Expiratory Flow Rate
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
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)
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)
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
Viral Load (in Nasal Lavage Samples)
Peak during infection (up to day 14)
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.

Full Information

First Posted
January 12, 2016
Last Updated
February 9, 2021
Sponsor
Imperial College London
Collaborators
Medical Research Council, Atopix Therapeutics, Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02660489
Brief Title
Effect of OC459 on the Response to Rhinovirus Challenge in Asthma
Official Title
Effect of the CRTH2 Antagonist OC459 on the Response to Rhinovirus Challenge in Asthma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
February 2018 (Actual)
Study Completion Date
February 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
Medical Research Council, Atopix Therapeutics, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Rhinovirus, Picornaviridae Infections, Common Cold
Keywords
CRTH2 antagonist, Prostaglandin D2 receptor, Anti-Asthmatic Agents, OC459, Allergic asthma, Eosinophilia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OC459 (CRTH2 antagonist)
Arm Type
Experimental
Arm Description
OC459 50mg once daily for 5 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet once daily for 5 weeks
Intervention Type
Drug
Intervention Name(s)
OC459
Other Intervention Name(s)
OC000459
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Other
Intervention Name(s)
Rhinovirus
Intervention Description
Inoculation with rhinovirus serotype 16
Primary Outcome Measure Information:
Title
Total Lower Respiratory Symptom Score
Description
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.
Time Frame
During 14 days following rhinovirus inoculation
Secondary Outcome Measure Information:
Title
Change in Asthma Control Questionnaire (ACQ)-6 Score
Description
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.
Time Frame
Baseline, 10 days post rhinovirus inoculation
Title
Percentage Change in Peak Expiratory Flow Rate
Description
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
Time Frame
Baseline and up to 14 days post rhinovirus inoculation
Title
Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
Time Frame
Baseline and up to 14 days post rhinovirus inoculation
Title
Change in Exhaled Nitric Oxide (FeNO)
Description
Percentage change from baseline (rhinovirus inoculation, day 0) to peak during infection (highest of measurements on days 3, 5, 7, 10 post inoculation)
Time Frame
Baseline and up to 10 days post rhinovirus inoculation
Title
Changes in Airway Hyper Responsiveness (Histamine)
Description
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
Time Frame
Baseline and 7 days post rhinovirus inoculation
Title
Viral Load (in Nasal Lavage Samples)
Description
Peak during infection (up to day 14)
Time Frame
Up to 14 days post rhinovirus inoculation
Title
Total Upper Respiratory Symptom Score
Description
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.
Time Frame
During 14 days following rhinovirus inoculation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sebastian L Johnston, MBBS PhD
Organizational Affiliation
National Heart & Lung Institute, Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Mary's Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
W2 1PG
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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Effect of OC459 on the Response to Rhinovirus Challenge in Asthma

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