Aspirin-exacerbated Respiratory Disease
Conditions
Brief summary
Subjects with physician-diagnosed aspirin-exacerbated respiratory disease (AERD) who remain unacceptably symptomatic with a SNOT 22 score \> 18 despite routine medical therapy will be enrolled in this single center, single-blinded study assessing the efficacy of dupilumab in AERD.
Detailed description
This is a single blind, placebo controlled trial to be conducted in adult patients with AERD to determine the efficacy and safety of dupilumab in treating symptoms of chronic rhinosinusitis. All subjects will be treated with the FDA-approved and the commercially available dose for adult atopic dermatitis of 300 mg every 2 weeks administered subcutaneously, based on the observed efficacy and safety of this dose. In addition to atopic dermatitis, this dose has also been shown to be efficacious in adult asthma.15 Patients will not be treated with a loading dose since other studies of dupilumab in asthma and chronic rhinosinusitis with nasal polyposis have not used a loading dose. There will be a one month screening period to determine the patient's eligibility and establish symptom control and baseline parameters. Patients will continue their background medications for chronic rhinosinusitis with nasal polyposis and asthma. These medications may include nasal corticosteroids, nasal antihistamines, systemic antihistamines, leukotriene receptor antagonists, 5 lipo-oxygenase inhibitors, inhaled corticosteroids, long-acting beta agonists, and long acting muscarinic antagonists. These controller medications will not be dispensed or supplied by the sponsor.
Interventions
DRUGDupilumab
dupilumab 300 mg subcutaneous injection every 2 weeks
Sponsors
Rochester General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Patients 18 years and older with a physician diagnosis of aspirin-exacerbated respiratory disease, as defined by a physician diagnosis of asthma, chronic rhinosinusitis with nasal polyposis, and a convincing clinical history of NSAID sensitivity 2. All subjects must have a SNOT 22 score ≥ 19 despite standard medical therapy. This minimal SNOT 22 was calculated by taking the range of SNOT 22 scores in studies of normal controls plus 8.9, which is the minimal clinically meaningful improvement in SNOT 22 score detected by patients. 3. Able to understand and willingness to sign informed consent 4. Able to comply with study procedures
Exclusion criteria
1. Patient \< 18 years of age 2. Pregnancy or breast feeding 3. Current tobacco use 4. Significant, uncontrolled medical conditions 5. Ongoing malignancy or history of malignancy in remission within the past 12 months 6. Current treatment with immunosuppressive medications except chronic oral steroids 7. Currently increasing dose of aeroallergen immunotherapy (patients on stable dose of aeroallergen immunotherapy will be allowed to participate) 8. Treatment with omalizumab, reslizumab, mepolizumab within 4 months of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SNOT 22 Score | From baseline to completion of study(7 months total) | This is a patient-reported outcome score for chronic rhinosinusitis with or without nasal polyposis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lund Mackay score | From baseline to completion of study( 7 months total) | Objective score for CT sinus imaging, this is a widely used method for radiologic staging of chronic rhinosinusitis. |
| ACT score | From baseline to completion of study( 7 months total) | Validated asthma control test, a series of 5 questions related to patient's asthma control over the previous 4 weeks. |
| Asthma Mini-AQLQ, 15 questions to assess quality of life. This assessment takes approximately 4-5 minutes to complete the questions. | From baseline to completion of study( 7 months total) | Validated asthma quality of life score |
| Change in FEV1 | From baseline to completion of study( 7 months total) | Forced expiratory volume in first second from spirometry |
| Change in FeNO | From baseline to completion of study( 7 months total) | Exhaled nitric oxide |
| Eosinophil count | From baseline to completion of study( 7 months total) | Absolute eosinophil count |
| UPSIT | From baseline to completion of study( 7 months total) | Univ. of Pennsylvania smell identification test |
| Serum tryptase | From baseline to completion of study( 7 months total) | Biomarker |
| Serum TARC (thymus and activation regulated cytokine) | From baseline to completion of study( 7 months total) | Biomarker |
| Serum prostaglandin D2 | From baseline to completion of study( 7 months total) | Biomarker |
| 24 hour urinary leukotriene E4 | From baseline to completion of study( 7 months total) | Biomarker |
| To assess the safety and tolerability of dupilumab | From baseline to completion of study( 7 months total) | Adverse events |
| To assess cumulative dose of systemic steroids | From baseline to completion of study( 7 months total) | Impact on systemic steroids |
| Total serum IgE | From baseline to completion of study( 7 months total) | Total IgE |
Countries
United States
Outcome results
None listed