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

Nasal Polyps Clinical Trial

— MARINER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05575037
• Other study ID #: 2022P002407
• Secondary ID: U19AI095219
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2023
• Est. completion date: April 30, 2026

Study information

• Verified date: February 2024
• Source: Brigham and Women's Hospital
• Contact: Tanya M Laidlaw, MD
• Phone: 617-525-1034
• Email: tlaidlaw[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key 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.

Related Conditions & MeSH terms

• Aspirin-Exacerbated Respiratory Disease
• Aspirin-Sensitive Asthma With Nasal Polyps
• Asthma
• Asthma, Aspirin-Induced
• Nasal Polyps
• Polyps
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

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

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in UPSIT.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in Rhinoscopic Total Polyp Score (TPS)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in TPS.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in Peak Nasal Inspiratory Flow (PNIF)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in PNIF.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in 22-Item Sino-Nasal Outcome Test (SNOT-22)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in SNOT-22.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in lung function - Forced Expiratory Volume 1 (FEV1)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in FEV1.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in Asthma control - Asthma Control Questionnaire-6 (ACQ-6)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in ACQ-6.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in Nasal fluid levels of eicosanoids	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid eicosanoid levels.	weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in Nasal fluid levels of albumin	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid albumin levels.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in urinary levels of eicosanoids	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in urinary eicosanoid levels.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in serum tryptase	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in serum tryptase levels.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in IgE levels	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid and plasma levels of IgE.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Other	Change in eosinophilic cationic protein (ECP)	Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid levels of ECP.	2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Primary	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	Nasal fluid levels of albumin	The nasal fluid levels of albumin will be measured at week 8 and serve as a surrogate biomarker of nasal epithelial cell integrity.	At Week 8 (Visit 3)
Secondary	Sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)	Patients' sense of smell will be assessed at week 8 using the UPSIT.	At Week 8 (Visit 3)
Secondary	Rhinoscopic Total Polyp Score (TPS)	The extent of patients' nasal polyps will be assessed at week 8 using a TPS.	At Week 8 (Visit 3)
Secondary	Peak Nasal Inspiratory Flow (PNIF)	Patients' nasal congestion will be assessed at week 8 by a PNIF.	At Week 8 (Visit 3)
Secondary	Quality of life - 22-Item Sino-Nasal Outcome Test (SNOT-22)	Quality of life will be assessed at week 8 with a SNOT-22.	At Week 8 (Visit 3)
Secondary	Lung function - Forced Expiratory Volume 1 (FEV1)	Patients' lung function will be assessed at week 8 with an FEV1.	At Week 8 (Visit 3)
Secondary	Asthma control - Asthma Control Questionnaire-6 (ACQ-6)	Asthma control will be measured at week 8 with an ACQ-6.	At Week 8 (Visit 3)
Secondary	Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation	Safety will be measured by the number of treatment-related AEs and SAEs leading to dupilumab discontinuation.	At Week 8 (Visit 3)