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

NCT05575037 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022P002407U19AI095219
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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 Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) and Aspirin-Exacerbated Respiratory Disease (AERD).

Conditions

Nasal Polyps; Asthma, Aspirin-Induced; Aspirin-Exacerbated Respiratory Disease; Aspirin-Sensitive Asthma With Nasal Polyps

Outcome Measures

Primary Outcomes (1)

• Nasal fluid levels of LTE4

  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.

  At Week 8 (Visit 3)

Secondary Outcomes (8)

• Nasal fluid levels of albumin

  At Week 8 (Visit 3)

• Sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)

  At Week 8 (Visit 3)

• Rhinoscopic Total Polyp Score (TPS)

  At Week 8 (Visit 3)

• Peak Nasal Inspiratory Flow (PNIF)

  At Week 8 (Visit 3)

• Quality of life - 22-Item Sino-Nasal Outcome Test (SNOT-22)

  At Week 8 (Visit 3)

Other Outcomes (12)

• Change in sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)

  2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

• Change in Rhinoscopic Total Polyp Score (TPS)

  2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

• Change in Peak Nasal Inspiratory Flow (PNIF)

  2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

Study Arms (1)

Dupilumab

EXPERIMENTAL

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

Drug: Dupilumab

Interventions

Dupilumab DRUG

8-week trial of dupilumab (an anti-IL-4a) in patients with AERD.

Also known as: Dupilumab Prefilled Syringe [Dupixent]

Dupilumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of AERD, defined as meeting the diagnostic triad with:
• History of physician-diagnosed asthma and
• History of physician-diagnosed nasal polyposis and
• History of pathognomonic reactions to aspirin or other nonselective COX inhibitors.
• Visible nasal polyps bilaterally on otoscope physical exam at the time of screening.
• Evidence of sense of smell impairment, with a University of Pennsylvania Smell Identification Test (UPSIT) score of \<34.
• 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).
• Consistent (daily) use of an intranasal steroid for at least 4 weeks prior to Screening.
• No current smoking (not more than one instance of smoking in the last 3 months).
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Nasal Polyps; Asthma, Aspirin-Induced

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Asthma; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Study Officials

• Tanya M Laidlaw, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 12, 2022
• Study Start: August 1, 2023
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)