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Active, Not Recruiting

NCT Number: NCT05575037

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

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).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

About this study

The protocol involves an 8-week study of dupilumab in patients with CRSwNP and/or 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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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

Note: Other inclusion and exclusion criteria apply.

Treatment and study plan

Dupilumab

Drug

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

Other names: Dupilumab Prefilled Syringe [Dupixent]

Primary outcomes

  1. Nasal fluid levels of LTE4

    Time frame: 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 outcomes

  1. Nasal fluid levels of albumin

    Time frame: 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.

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

    Time frame: At Week 8 (Visit 3)

    Patients' sense of smell will be assessed at week 8 using the UPSIT. The UPSIT scale goes from 0 to 40, with 0 being worse (no scents identified) and 40 being best (all scents identified)

  3. Rhinoscopic Total Polyp Score (TPS)

    Time frame: At Week 8 (Visit 3)

    The extent of patients' nasal polyps will be assessed at week 8 using a TPS. The TPS scale goes from 0 (no polyps) to 8 (large polyps bilaterally), with 0 being best and 8 being worst.

  4. Peak Nasal Inspiratory Flow (PNIF)

    Time frame: At Week 8 (Visit 3)

    Patients' nasal congestion will be assessed at week 8 by a PNIF. PNIF goes from 0 mL (no airflow) to 500 mL of airflow, with 0 being worst.

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

    Time frame: At Week 8 (Visit 3)

    Quality of life will be assessed at week 8 with a SNOT-22. For the SNOT-22, the scores range from 0 (no symptoms, excellent disease control) to 110 (maximum sinus symptoms, poor disease control).

  6. Lung function - Forced Expiratory Volume 1 (FEV1)

    Time frame: At Week 8 (Visit 3)

    Patients' lung function will be assessed at week 8 with an FEV1.

  7. Asthma control - Asthma Control Questionnaire-6 (ACQ-6)

    Time frame: At Week 8 (Visit 3)

    Asthma control will be measured at week 8 with an ACQ-6. For the ACQ-6, scores ranging from 0 (well-controlled) to 6 (extremely poorly-controlled). A lower score indicates better asthma control.

  8. Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation

    Time frame: At Week 8 (Visit 3)

    Safety will be measured by the number of treatment-related AEs and SAEs leading to dupilumab discontinuation.

Other outcomes

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

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in UPSIT. The UPSIT scale goes from 0 to 40, with 0 being worse (no scents identified) and 40 being best (all scents identified)

  2. Change in Rhinoscopic Total Polyp Score (TPS)

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in TPS. The TPS scale goes from 0 (no polyps) to 8 (large polyps bilaterally), with 0 being best and 8 being worst.

  3. Change in Peak Nasal Inspiratory Flow (PNIF)

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in PNIF. PNIF goes from 0 mL (no airflow) to 500 mL of airflow, with 0 being worst.

  4. Change in 22-Item Sino-Nasal Outcome Test (SNOT-22)

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in SNOT-22. For the SNOT-22, the scores range from 0 (no symptoms, excellent disease control) to 110 (maximum sinus symptoms, poor disease control).

  5. Change in lung function - Forced Expiratory Volume 1 (FEV1)

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in FEV1.

  6. Change in Asthma control - Asthma Control Questionnaire-6 (ACQ-6)

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in ACQ-6. For the ACQ-6, scores ranging from 0 (well-controlled) to 6 (extremely poorly-controlled). A lower score indicates better asthma control.

  7. Change in Nasal fluid levels of eicosanoids

    Time frame: weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid eicosanoid levels.

  8. Change in Nasal fluid levels of albumin

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid albumin levels.

  9. Change in urinary levels of eicosanoids

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in urinary eicosanoid levels.

  10. Change in serum tryptase

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in serum tryptase levels.

  11. Change in IgE levels

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid and plasma levels of IgE.

  12. Change in eosinophilic cationic protein (ECP)

    Time frame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

    Change from Visit 1 to Visit 2 and from Visit 1 to Visit 3 in nasal fluid levels of ECP.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

Registry information

Official study title

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

Acronym: MARINER

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Oct 12, 2022
Registry last updated
Sep 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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