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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03028350

Enrollment

Registered

2017-01-23

Start date

2017-07-17

Completion date

2023-04-25

Last updated

2024-07-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma, Aspirin-Induced

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.

Interventions

DRUGPlacebo Oral Capsule

Subjects will be treated with oral placebo daily for 8 weeks

DRUGIfetroban Oral Capsule

Subjects will be treated with oral ifetroban daily for 8 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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

Other

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Ifetroban Oral Capsule Oral ifetroban, 200 mg daily for 8 weeks Ifetroban Oral Capsule: Subjects will be treated with oral ifetroban daily for 8 weeks	25
Placebo Oral Capsule Oral placebo daily for 8 weeks Placebo Oral Capsule: Subjects will be treated with oral placebo daily for 8 weeks	29
Total	54

Baseline characteristics

Characteristic	Ifetroban Oral Capsule	Total	Placebo Oral Capsule
Age, Continuous	55 years	51 years	45 years
BMI (kg/m2), Categorical >=30; <30 <30	14 Participants	33 Participants	19 Participants
BMI (kg/m2), Categorical >=30; <30 >=30	11 Participants	21 Participants	10 Participants
BMI (kg/m2), Continuous	28.8 kg/m^2	27.8 kg/m^2	27.0 kg/m^2
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	9 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants	45 Participants	25 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	4 Participants	10 Participants	6 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) White	19 Participants	41 Participants	22 Participants
Region of Enrollment United States	25 participants	54 participants	29 participants
Sex: Female, Male Female	14 Participants	34 Participants	20 Participants
Sex: Female, Male Male	11 Participants	20 Participants	9 Participants
Weight	84.2 kg	84.4 kg	85.4 kg

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 25	0 / 29
other Total, other adverse events	7 / 25	11 / 29
serious Total, serious adverse events	1 / 25	0 / 29

Outcome results

Primary

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.