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

August 12, 2026 updated by: Tanya Laidlaw, MD, Brigham and Women's Hospital

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dupilumab
Subjects will receive dupilumab (300mg every-other-week for 8 weeks).
Drug: Dupilumab
8-week trial of dupilumab (an anti-IL-4a) in patients with AERD.
Other Names:
  • Dupilumab Prefilled Syringe [Dupixent]

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
At Week 8 (Visit 3)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
At Week 8 (Visit 3)
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.
At Week 8 (Visit 3)
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.
At Week 8 (Visit 3)
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)
At Week 8 (Visit 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.
At Week 8 (Visit 3)
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.
At Week 8 (Visit 3)
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).
At Week 8 (Visit 3)
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.
At Week 8 (Visit 3)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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).
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
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.
2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Brigham and Women's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tanya M Laidlaw, MD, Brigham and Women's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 7, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022P002407
  • U19AI095219 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings