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

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).

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).

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.