Brief Summary
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.
Brief Title
Oral Ifetroban to Treat Aspirin Exacerbated Respiratory Disease (AERD)
Detailed Description
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Asthma, Aspirin-Induced
Eligibility Criteria
Inclusion Criteria:
1. History of physician-diagnosed asthma
2. History of nasal polyposis
3. 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.
4. Stable asthma (post-bronchodilator forced expiratory volume in 1 second (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).
5. ≥ 18 years of age
6. 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:
1. 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.
2. Current pregnancy or breastfeeding
3. Use of oral or systemic steroids (e.g. prednisone or equivalent) \> 20 mg daily in the last four weeks before starting treatment.
4. Daily use of long-acting antihistamines in the last two weeks before starting treatment.
5. 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).
6. Any use of nonsteroidal anti-inflammatory drugs (NSAIDs) or any drug that inhibits the cyclooxygenase enzyme in the last two weeks before starting treatment.
7. History of bleeding diathesis or use of anticoagulant or antiplatelet drugs in the last two weeks before starting treatment.
8. 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.
9. Endoscopic sinus surgery / polypectomy within the past three months
10. Previously treated in a clinical trial with ifetroban within the past three months.
11. Previously treated with other investigational drugs within eight weeks or five half-lives, whichever is longer, before screening
12. Conditions/concomitant disease which make them unevaluable for the efficacy endpoints
1. History of physician-diagnosed asthma
2. History of nasal polyposis
3. 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.
4. Stable asthma (post-bronchodilator forced expiratory volume in 1 second (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).
5. ≥ 18 years of age
6. 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:
1. 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.
2. Current pregnancy or breastfeeding
3. Use of oral or systemic steroids (e.g. prednisone or equivalent) \> 20 mg daily in the last four weeks before starting treatment.
4. Daily use of long-acting antihistamines in the last two weeks before starting treatment.
5. 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).
6. Any use of nonsteroidal anti-inflammatory drugs (NSAIDs) or any drug that inhibits the cyclooxygenase enzyme in the last two weeks before starting treatment.
7. History of bleeding diathesis or use of anticoagulant or antiplatelet drugs in the last two weeks before starting treatment.
8. 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.
9. Endoscopic sinus surgery / polypectomy within the past three months
10. Previously treated in a clinical trial with ifetroban within the past three months.
11. Previously treated with other investigational drugs within eight weeks or five half-lives, whichever is longer, before screening
12. Conditions/concomitant disease which make them unevaluable for the efficacy endpoints
Inclusion Criteria
Inclusion Criteria:
1. History of physician-diagnosed asthma
2. History of nasal polyposis
3. 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.
4. Stable asthma (post-bronchodilator forced expiratory volume in 1 second (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).
5. ≥ 18 years of age
6. 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.
1. History of physician-diagnosed asthma
2. History of nasal polyposis
3. 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.
4. Stable asthma (post-bronchodilator forced expiratory volume in 1 second (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).
5. ≥ 18 years of age
6. 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03028350
Org Class
Industry
Org Full Name
Cumberland Pharmaceuticals
Org Study Id
CPI-IFE-006
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Multicenter, Double-blind, Randomized, Placebo-Controlled Trial to Evaluate Oral Ifetroban in Subjects With Symptomatic Aspirin Exacerbated Respiratory Disease (AERD)
Primary Outcomes
Outcome Description
Sinonasal Outcome Test-22 (SNOT-22) score is a scale with a minimum score of 0 and a maximum score of 110 based on the presence and severity of symptoms and outcomes of rhinosinusitis. Higher scores indicate worse symptoms and/or outcomes.
Outcome Measure
Change From Baseline in Sinonasal Outcome Test-22 Score
Outcome Time Frame
Baseline and 8 weeks
Secondary Outcomes
Outcome Description
The Asthma Control Questionnaire-7 is a scoring system with a minimum score of 0 and a maximum score of 6 based on the severity and frequency of asthma symptoms. Higher scores indicate worse control of asthma symptoms.
Outcome Time Frame
Baseline and 8 weeks
Outcome Measure
Change From Baseline in Asthma Control Questionnaire -7 Score
Outcome Description
The Total Nasal Symptom Score is a scoring system with a minimum score of 0 and maximum score of 15 based on severity of nasal symptoms. Higher scores indicate worse nasal symptoms.
Outcome Time Frame
Baseline and 8 weeks
Outcome Measure
Change From Baseline in Total Nasal Symptom Score (Morning)
Outcome Description
Change From Baseline in Forced Expiratory Volume in 1 second (FEV1) at 8 weeks
Outcome Time Frame
Baseline and 8 weeks
Outcome Measure
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Outcome Description
Change From Baseline in Peak Nasal Inspiratory Flow Rate (PNIFR) at 8 weeks
Outcome Time Frame
Baseline and 8 weeks
Outcome Measure
Change From Baseline in Peak Nasal Inspiratory Flow Rate (PNIFR)
Outcome Description
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at 8 weeks
Outcome Time Frame
Baseline and 8 weeks
Outcome Measure
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
Outcome Description
The Total Nasal Symptom Score is a scale with a minimum score of 0 and maximum score of 15 based on severity of nasal symptoms. Higher scores indicate worse nasal symptoms.
Outcome Time Frame
Baseline and 8 weeks
Outcome Measure
Change From Baseline in Total Nasal Symptom Score (Afternoon/Evening)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Elina Jerschow
Investigator Email
EJERSCHO@montefiore.org
Investigator Phone
718-405-8075 / 917-362-5291