Mechanisms of Benefit of IL4RA Inhibition in Aspirin-Exacerbated Respiratory Disease

Phase 2

Recruiting

• Conditions: Asthma, Aspirin-Induced; Aspirin-Sensitive Asthma With Nasal Polyps; Nasal Polyps; Aspirin-Exacerbated Respiratory Disease
• Interventions: Drug: Dupilumab

• Registration Number: NCT05575037
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

The overall aim of the study is to determine the clinical efficacy and mechanisms of action of anti-IL-4a (dupilumab) as treatment for patients with Aspirin-Exacerbated Respiratory Disease (AERD).

Detailed Description

The protocol involves an 8-week trial of dupilumab in patients with AERD. Participants will have 4 total doses of dupilumab administered, with each dose administered every 2 weeks. There will be full clinical assessments and biospecimen collections at Baseline (Visit 1), Week 2 (Visit 2), and Week 8 (Visit 3).

Study Timeline

• Study First Submitted: 2022-10-07
• Study First Submitted QC: 2022-10-07
• Study First Posted: 2022-10-12
• Study Start: 2023-08-01
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-27
• Last Update Posted: 2024-02-28
• Primary Completion: 2026-04-30
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

1. History of AERD, defined as meeting the diagnostic triad with:

   1. History of physician-diagnosed asthma and
   2. History of physician-diagnosed nasal polyposis and
   3. History of pathognomonic reactions to aspirin or other nonselective COX inhibitors.

2. Visible nasal polyps bilaterally on otoscope physical exam at the time of screening.

3. Evidence of sense of smell impairment, with a University of Pennsylvania Smell Identification Test (UPSIT) score of <34.

4. Stable asthma (no glucocorticoid burst for at least 4 weeks prior to Visit 1, and no hospitalizations or ER visits for asthma for at least the prior 3 months).

5. Consistent (daily) use of an intranasal steroid for at least 4 weeks prior to Screening.

6. No current smoking (not more than one instance of smoking in the last 3 months).

7. For females: Practicing FDA-approved methods of birth control for the duration of the study. Female participants of childbearing potential must have a negative pregnancy test upon study entry.

Key

Exclusion Criteria

1. Use of investigational drugs within 12 weeks of Screening.
2. Use of any biologic agent within 4 months prior to Screening.
3. Use of systemic (enteral or injected) glucocorticoids within 4 weeks prior to Screening.
4. History of any sinonasal surgery within 4 months prior to Screening
5. Current use of zileuton
6. Current use of high-dose aspirin therapy (no more than 325 mg aspirin per day will be allowed)
7. Pregnant, nursing, or planning to become pregnant

Note: Other inclusion and exclusion criteria apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dupilumab	Dupilumab	Subjects will receive dupilumab (300mg every-other-week for 8 weeks).

Primary Outcome Measures

Name	Time	Method
Nasal fluid levels of LTE4	At Week 8 (Visit 3)	The nasal fluid levels of LTE4 will be measured at week 8 and will serve as a surrogate biomarker of respiratory mast cell activation or burden.

Secondary Outcome Measures

Name	Time	Method
Lung function - Forced Expiratory Volume 1 (FEV1)	At Week 8 (Visit 3)	Patients' lung function will be assessed at week 8 with an FEV1.
Rhinoscopic Total Polyp Score (TPS)	At Week 8 (Visit 3)	The extent of patients' nasal polyps will be assessed at week 8 using a TPS.
Peak Nasal Inspiratory Flow (PNIF)	At Week 8 (Visit 3)	Patients' nasal congestion will be assessed at week 8 by a PNIF.
Asthma control - Asthma Control Questionnaire-6 (ACQ-6)	At Week 8 (Visit 3)	Asthma control will be measured at week 8 with an ACQ-6.
Quality of life - 22-Item Sino-Nasal Outcome Test (SNOT-22)	At Week 8 (Visit 3)	Quality of life will be assessed at week 8 with a SNOT-22.
Sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)	At Week 8 (Visit 3)	Patients' sense of smell will be assessed at week 8 using the UPSIT.
Nasal fluid levels of albumin	At Week 8 (Visit 3)	The nasal fluid levels of albumin will be measured at week 8 and serve as a surrogate biomarker of nasal epithelial cell integrity.
Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation	At Week 8 (Visit 3)	Safety will be measured by the number of treatment-related AEs and SAEs leading to dupilumab discontinuation.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States