Aspirin-Exacerbated Respiratory Disease, Aspirin-Sensitive Asthma With Nasal Polyps, Asthma, Aspirin-Induced, Nasal Polyps
Conditions
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).
Interventions
DRUGDupilumab
8-week trial of dupilumab (an anti-IL-4a) in patients with AERD.
Sponsors
Brigham and Women's Hospital
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nasal fluid levels of LTE4 | 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
| Measure | Time frame | Description |
|---|---|---|
| Nasal fluid levels of albumin | 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. |
| Sense of smell - University of Pennsylvania Smell Identification Test (UPSIT) | 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) |
| Rhinoscopic Total Polyp Score (TPS) | 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. |
| Peak Nasal Inspiratory Flow (PNIF) | 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. |
| Quality of life - 22-Item Sino-Nasal Outcome Test (SNOT-22) | 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). |
| Lung function - Forced Expiratory Volume 1 (FEV1) | At Week 8 (Visit 3) | Patients' lung function will be assessed at week 8 with an FEV1. |
| Asthma control - Asthma Control Questionnaire-6 (ACQ-6) | 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. |
| Number of treatment-related adverse events (AEs) and serious adverse events (SAEs) leading to study drug discontinuation | At Week 8 (Visit 3) | Safety will be measured by the number of treatment-related AEs and SAEs leading to dupilumab discontinuation. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTanya M Laidlaw, MD
Brigham and Women's Hospital
Outcome results
None listed