Oral Ifetroban to Treat Aspirin Exacerbated Respiratory Disease (AERD)

Phase 2

Completed

• Conditions: Asthma, Aspirin-Induced
• Interventions: Drug: Ifetroban Oral Capsule; Drug: Placebo Oral Capsule

• Registration Number: NCT03028350
• Lead Sponsor: Cumberland Pharmaceuticals

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.

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.

Study Timeline

• Study First Submitted: 2017-01-19
• Study First Submitted QC: 2017-01-19
• Study First Posted: 2017-01-23
• Study Start: 2017-07-17
• Primary Completion: 2023-04-25
• Study Completion: 2023-04-25
• Status Verified: 2024-06
• Results First Submitted: 2024-06-05
• Results First Submitted QC: 2024-06-05
• Last Update Submitted: 2024-06-27
• Results First Posted: 2024-06-28
• Last Update Posted: 2024-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ifetroban Oral Capsule	Ifetroban Oral Capsule	Oral ifetroban, 200 mg daily for 8 weeks
Placebo Oral Capsule	Placebo Oral Capsule	Oral placebo daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Sinonasal Outcome Test-22 Score	Baseline and 8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Total Nasal Symptom Score (Morning)	Baseline and 8 weeks	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.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	Baseline and 8 weeks	Change From Baseline in Forced Expiratory Volume in 1 second (FEV1) at 8 weeks
Change From Baseline in Asthma Control Questionnaire -7 Score	Baseline and 8 weeks	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.
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)	Baseline and 8 weeks	Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at 8 weeks
Change From Baseline in Total Nasal Symptom Score (Afternoon/Evening)	Baseline and 8 weeks	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.
Change From Baseline in Peak Nasal Inspiratory Flow Rate (PNIFR)	Baseline and 8 weeks	Change From Baseline in Peak Nasal Inspiratory Flow Rate (PNIFR) at 8 weeks

Trial Locations

Locations (16)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Emory University School of Medicine, Sinus, Nasal, and Allergy Center; 🇺🇸 Atlanta, Georgia, United States

Scripps Clinic - Carmel Valley; 🇺🇸 San Diego, California, United States

Kansas City Allergy and Asthma Associates, PA; 🇺🇸 Overland Park, Kansas, United States

Banner University of Arizona Medical Center, Asthma & Airway Disease Research Center; 🇺🇸 Tucson, Arizona, United States

Antelope Valley Clinical Trials; 🇺🇸 Lancaster, California, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Deaconess Clinic; 🇺🇸 Evansville, Indiana, United States

Rochester Regional Health; 🇺🇸 Rochester, New York, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Virginia Medical Center; 🇺🇸 Charlottesville, Virginia, United States

The Research Center; 🇺🇸 Hialeah, Florida, United States

Advanced ENT & Allergy; 🇺🇸 Louisville, Kentucky, United States

Wake Forest Baptist Health; 🇺🇸 Winston-Salem, North Carolina, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States