NCT05575037Active, not recruitingPhase 2
Mechanisms of Benefit of IL4RA Inhibition in Aspirin-Exacerbated Respiratory Disease: MARINER
Brigham and Women's Hospital1 site in 1 country17 target enrollmentStarted: August 1, 2023Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Nasal fluid levels of LTE4
Study Overview
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).
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 <
- •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.
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.
Arms & Interventions
Dupilumab
Experimental
Subjects will receive dupilumab (300mg every-other-week for 8 weeks).
Intervention: Dupilumab (Drug)
Outcomes
Primary Outcomes
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
- 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))
- Quality of life - 22-Item Sino-Nasal Outcome Test (SNOT-22)(At Week 8 (Visit 3))
- Lung function - Forced Expiratory Volume 1 (FEV1)(At Week 8 (Visit 3))
- Asthma control - Asthma Control Questionnaire-6 (ACQ-6)(At Week 8 (Visit 3))
- Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation(At Week 8 (Visit 3))
- Rhinoscopic Total Polyp Score (TPS)(At Week 8 (Visit 3))
- 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))
- 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))
- Lung function - Forced Expiratory Volume 1 (FEV1)(At Week 8 (Visit 3))
- Asthma control - Asthma Control Questionnaire-6 (ACQ-6)(At Week 8 (Visit 3))
- Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation(At Week 8 (Visit 3))
Investigators
Tanya Laidlaw, MD
Associate Professor of Medicine
Brigham and Women's Hospital
Study Sites (1)
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