Clinical trial NCT03028350: Oral Ifetroban to Treat Aspirin Exacerbated Respiratory Disease (AERD)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma, Aspirin-Induced
Lead sponsor: Cumberland Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-01-23
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Sinonasal Outcome Test-22 Score
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Change From Baseline in Asthma Control Questionnaire -7 Score
timeFrame: Baseline and 8 weeks
measure: Change From Baseline in Total Nasal Symptom Score (Morning)
timeFrame: Baseline and 8 weeks
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and 8 weeks
measure: Change From Baseline in Peak Nasal Inspiratory Flow Rate (PNIFR)
timeFrame: Baseline and 8 weeks
measure: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: Baseline and 8 weeks
measure: Change From Baseline in Total Nasal Symptom Score (Afternoon/Evening)
timeFrame: Baseline and 8 weeks
Other outcomes:
measure: Change From Baseline in Blood Eosinophil Count
timeFrame: Baseline and 8 weeks
Locations:
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center, Asthma & Airway Disease Research Center
state: Arizona
city: Lancaster
country: United States
facility: Antelope Valley Clinical Trials
state: California
city: San Diego
country: United States
facility: Scripps Clinic - Carmel Valley
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Hialeah
country: United States
facility: The Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine, Sinus, Nasal, and Allergy Center
state: Georgia
city: Evansville
country: United States
facility: Deaconess Clinic
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Allergy and Asthma Associates, PA
state: Kansas
city: Louisville
country: United States
facility: Advanced ENT & Allergy
state: Kentucky
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester Regional Health
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
Study officials:
affiliation: Scripps Research Institute
name: Andrew White, MD
role: PRINCIPAL_INVESTIGATOR
References: