Oral Ifetroban to Treat Aspirin Exacerbated Respiratory Disease (AERD)

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma, Aspirin-Induced
• Intervention / Treatment: Drug: Ifetroban Oral Capsule; Drug: Placebo Oral Capsule

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University of Arizona Medical Center, Asthma & Airway Disease Research Center
  • California
    • Lancaster, California, United States, 93534
      • Antelope Valley Clinical Trials
    • San Diego, California, United States, 92130
      • Scripps Clinic - Carmel Valley
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Hialeah, Florida, United States, 33013
      • The Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University School of Medicine, Sinus, Nasal, and Allergy Center
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Allergy and Asthma Associates, PA
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Advanced ENT & Allergy
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Rochester, New York, United States, 14607
      • Rochester Regional Health
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest Baptist Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9035
      • UT Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ifetroban Oral Capsule; Oral ifetroban, 200 mg daily for 8 weeks	Drug: Ifetroban Oral Capsule; Subjects will be treated with oral ifetroban daily for 8 weeks; Other Names: Ifetroban
Placebo Comparator: Placebo Oral Capsule; Oral placebo daily for 8 weeks	Drug: Placebo Oral Capsule; Subjects will be treated with oral placebo daily for 8 weeks; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sinonasal Outcome Test-22 Score	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.	Baseline and 8 weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Blood Eosinophil Count	Change From Baseline in Blood Eosinophil Count at 8 Weeks	Baseline and 8 weeks

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Principal Investigator: Andrew White, MD, Scripps Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2017
• Primary Completion (Actual): April 25, 2023
• Study Completion (Actual): April 25, 2023

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 19, 2017
• First Posted (Estimated): January 23, 2017

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Immune System Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Drug Hypersensitivity; Asthma; Respiration Disorders; Respiratory Tract Diseases; Asthma, Aspirin-Induced; Platelet Aggregation Inhibitors; Ifetroban
• Other Study ID Numbers: CPI-IFE-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No