Oral Ifetroban to Treat Aspirin Exacerbated Respiratory Disease (AERD)

Study Overview
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Brief Summary
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The purpose of this phase 2 study is to assess the safety and efficacy of oral ifetroban for the treatment of aspirin-exacerbated respiratory disease (AERD). AERD is a disease that involves asthma, recurring nasal polyps, and respiratory reactions to aspirin and other nonsteroidal anti-inflammatory drugs.

Detailed Description
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This is a randomized, placebo-controlled, double-blind phase 2 trial evaluating approximately 76 subjects with symptomatic AERD on the safety and efficacy of 8 weeks of oral ifetroban treatment. Eligible AERD subjects will be randomized to receive 8 weeks of either oral ifetroban daily or matching placebo followed by a 2-week post-treatment period.

Official Title
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A Phase 2 Multicenter, Double-blind, Randomized, Placebo-Controlled Trial to Evaluate Oral Ifetroban in Subjects With Symptomatic Aspirin Exacerbated Respiratory Disease (AERD)

Conditions
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Asthma, Aspirin-Induced

Intervention / Treatment
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* Drug: Ifetroban Oral Capsule
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of physician-diagnosed asthma History of nasal polyposis History of at least two reactions to oral aspirin or other nonselective cyclooxygenase inhibitor with features of lower airway involvement (cough, chest tightness, wheezing, dyspnea), or one reaction that was life-threatening and required hospitalization, or a diagnosis of AERD by a physician-conducted challenge to aspirin in the last five years before starting treatment. Stable asthma (post-bronchodilator FEV1 of ≥ 60%, no glucocorticoid burst for at least two weeks prior to starting treatment, no hospitalizations or emergency room visits for asthma at least three months prior to starting treatment and not on a dose >1000 µg fluticasone or equivalent daily). ≥ 18 years of age Exhibit symptomatic AERD within three weeks of starting treatment by demonstrating a score of at least 20 on the Sino-nasal Outcome Test (SNOT) - 22. Exclusion Criteria: Current smoking, defined as daily tobacco smoking in the last six months and at least one instance of tobacco smoking in the last three months. Current pregnancy or breastfeeding Use of oral or systemic steroids (e.g. prednisone or equivalent) > 20 mg daily in the last four weeks before starting treatment. Daily use of long-acting antihistamines in the last two weeks before starting treatment. Less than 12 months of allergy shots (maintenance dose of allergy shots are allowed if treatment duration exceeds 12 months). Less than 1 month of 5-lipoxygenase inhibitors (e.g. zileuton) and/or leukotriene receptor antagonists (e.g. montelukast). Any use of nonsteroidal anti-inflammatory drugs (NSAIDs) or any drug that inhibits the cyclooxygenase enzyme in the last two weeks before starting treatment. History of bleeding diathesis or use of anticoagulant or antiplatelet drugs in the last two weeks before starting treatment. Any immunosuppressive treatment including but not limited to methotrexate, cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, azathioprine, and cyclophosphamide in the last two weeks before starting treatment (maintenance dose of allergy shots are allowed if treatment duration exceeds 12 months). Biologics/immunotherapies such as Xolair or Nucala are permitted if duration exceeds three months. Endoscopic sinus surgery / polypectomy within the past three months Previously treated in a clinical trial with ifetroban within the past three months. Previously treated with other investigational drugs within eight weeks or five half-lives, whichever is longer, before screening Conditions/concomitant disease which make them unevaluable for the efficacy endpoints

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ifetroban Oral Capsule<br>Oral ifetroban, 200 mg daily for 8 weeks | Drug: Ifetroban Oral Capsule<br>* Subjects will be treated with oral ifetroban daily for 8 weeks<br>* Other names: Ifetroban;|
| Placebo Comparator: Placebo Oral Capsule<br>Oral placebo daily for 8 weeks | Drug: Placebo Oral Capsule<br>* Subjects will be treated with oral placebo daily for 8 weeks<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Sino-Nasal Outcome Test-22 score |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Asthma Control Questionnaire -7 score |  | 8 weeks | 
| Change From Baseline in Total Nasal Symptom score |  | 8 weeks | 
| Change From Baseline in FEV1 |  | 8 weeks | 
| Change From Baseline in PNIFR |  | 8 weeks | 
| Change From Baseline in FeNO |  | 8 weeks | 
| Change From Baseline in rescue medication |  | 8 weeks | 
| Change From Baseline in antibiotic use |  | 8 weeks |