Effect of OC000459 on Eosinophilic Airway Inflammation in Severe Asthma

Study Overview
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Brief Summary
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The aim is to study the effect of OC000459 on eosinophilic airway inflammation and asthma control in subjects with severe, refractory eosinophilic asthma.

Detailed Description
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At week 12 subjects not on oral corticosteroids (OCS) will complete the treatment period and return after 4 weeks for final follow up visit. Those subjects who were taking OCS at baseline will continue for a maximum of 12 additional weeks, double blind period during which their current OCS treatment will be titrated down according to their clinical response.

Official Title
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The Effect of OC000459 on Eosinophilic Airway Inflammation and Asthma Control in Subjects With Refractory Eosinophilic Asthma: a Randomised, Double-blind, Placebo Controlled Trial

Conditions
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Severe Eosinophilic Asthma

Intervention / Treatment
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* Drug: OC000459
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Show evidence of reversible airflow obstruction documented within the previous 12 months or prior to Randomisation. Meet the European Respiratory Society/American Thoracic Society (ERS/ATS) criteria for severe asthma at Screening. Have documented evidence of eosinophilic airway inflammation during the 12 months prior to Screening. Have evidence of eosinophilic airway inflammation at Screening as reflected by an induced sputum eosinophil count of ≥3%. Subjects who are taking oral corticosteroids (OCS) must be receiving a 20 mg prednisolone equivalent dose, or less, daily for at least four weeks before the first dose of study drug. The dose of OCS should be unchanged for at least 14 days prior to the Baseline visit. Exclusion Criteria: Treatment with XolairTM or anti-Th2 biologicals within 6 months prior to screening. Subjects with clinically significant abnormal serum biochemistry, haematology and urine examination values Subjects who have been hospitalised in the last 3 months. History of more than 2 episodes of confirmed bacterial lower respiratory tract infection or current lower respiratory tract infection. Subjects are current smokers or have a smoking history of >15 pack years. Significant comorbidity that in the Investigator's opinion is likely to impact the subject's participation in a 26 week study. Presence of a clinically important lung condition other than asthma, malignancy or previous history of cancer in remission for less than 12 months, clinically important liver or kidney disease, uncontrolled clinically significant cardiovascular disease, hypereosinophilic syndromes such as Churg-Strauss Syndrome or eosinophilic oesophagitis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OC000459<br>Once daily dose of 50mg OC000459 tablets orally for 12/24 weeks | Drug: OC000459<br> <br> |
| Placebo Comparator: Placebo<br>Once daily dose of placebo tablets orally for 12/24 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effect of OC000459 50mg given once daily with placebo on the induced sputum eosinophil counts. |  | Mean change from baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect on pre- and post-bronchodilator spirometry using forced expiratory volume in one second (FEV1). |  | Every 4 weeks up to week 12 | 
| The effect of OC000459 on fractional exhaled nitric oxide (FeNO). |  | At 4,8 and 12 weeks | 
| Measuring quality of life using standardised asthma quality of life questionnaire (AQLQ(S)). |  | At weeks 4,8 and 12 | 
| Statistical comparison from baseline on induced sputum eosinophil count. |  | At weeks 4,8 and 12 |