Clinical trial NCT05575037: Mechanisms of Benefit of IL4RA Inhibition in Aspirin-Exacerbated Respiratory Disease
Official title: Mechanisms of Benefit of IL4RA Inhibition in Aspirin-Exacerbated Respiratory Disease: MARINER
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nasal Polyps
Asthma, Aspirin-Induced
Aspirin-Exacerbated Respiratory Disease
Aspirin-Sensitive Asthma With Nasal Polyps
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-10-12
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 Aspirin-Exacerbated Respiratory Disease (AERD).

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Nasal fluid levels of LTE4
timeFrame: At Week 8 (Visit 3)
Secondary outcomes:
measure: Nasal fluid levels of albumin
timeFrame: At Week 8 (Visit 3)
measure: Sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: At Week 8 (Visit 3)
measure: Rhinoscopic Total Polyp Score (TPS)
timeFrame: At Week 8 (Visit 3)
measure: Peak Nasal Inspiratory Flow (PNIF)
timeFrame: At Week 8 (Visit 3)
measure: Quality of life - 22-Item Sino-Nasal Outcome Test (SNOT-22)
timeFrame: At Week 8 (Visit 3)
measure: Lung function - Forced Expiratory Volume 1 (FEV1)
timeFrame: At Week 8 (Visit 3)
measure: Asthma control - Asthma Control Questionnaire-6 (ACQ-6)
timeFrame: At Week 8 (Visit 3)
measure: Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation
timeFrame: At Week 8 (Visit 3)
Other outcomes:
measure: Change in sense of smell - University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in Rhinoscopic Total Polyp Score (TPS)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in Peak Nasal Inspiratory Flow (PNIF)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in 22-Item Sino-Nasal Outcome Test (SNOT-22)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in lung function - Forced Expiratory Volume 1 (FEV1)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in Asthma control - Asthma Control Questionnaire-6 (ACQ-6)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in Nasal fluid levels of eicosanoids
timeFrame: weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in Nasal fluid levels of albumin
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in urinary levels of eicosanoids
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in serum tryptase
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in IgE levels
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
measure: Change in eosinophilic cationic protein (ECP)
timeFrame: 2 weeks (between Visit 1 and Visit 2) and 8 weeks (between Visit 1 and Visit 3)
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Tanya M Laidlaw, MD
role: PRINCIPAL_INVESTIGATOR
References: