Dupilumab for Aspirin-exacerbated Respiratory Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Dupilumab as add-on Therapy for Aspirin-exacerbated Respiratory Disease (AERD)

Conditions
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Aspirin-exacerbated Respiratory Disease

Intervention / Treatment
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* Drug: Dupilumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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. Able to understand and willingness to sign informed consent Able to comply with study procedures Exclusion Criteria: Patient < 18 years of age Pregnancy or breast feeding Current tobacco use Significant, uncontrolled medical conditions Ongoing malignancy or history of malignancy in remission within the past 12 months Current treatment with immunosuppressive medications except chronic oral steroids Currently increasing dose of aeroallergen immunotherapy (patients on stable dose of aeroallergen immunotherapy will be allowed to participate) Treatment with omalizumab, reslizumab, mepolizumab within 4 months of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>Single-blinded, Dupilumab or matching placebo will be administered to the patients at the study visits. At each study visit, a single dose of dupilumab or placebo will be dispensed to the patients to be administered at home. 300 mg/2 ml solution in a single-dose pre-filled syringe with needle shield given once every 2 weeks in a subcutaneous injection | Drug: Dupilumab<br>* dupilumab 300 mg subcutaneous injection every 2 weeks<br>* Other names: Matching placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNOT 22 Score | This is a patient-reported outcome score for chronic rhinosinusitis with or without nasal polyposis | From baseline to completion of study(7 months total) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPSIT | Univ. of Pennsylvania smell identification test | From baseline to completion of study( 7 months total) | 
| Lund Mackay score | Objective score for CT sinus imaging, this is a widely used method for radiologic staging of chronic rhinosinusitis. | From baseline to completion of study( 7 months total) | 
| ACT score | Validated asthma control test, a series of 5 questions related to patient's asthma control over the previous 4 weeks. | From baseline to completion of study( 7 months total) | 
| Asthma Mini-AQLQ, 15 questions to assess quality of life. This assessment takes approximately 4-5 minutes to complete the questions. | Validated asthma quality of life score | From baseline to completion of study( 7 months total) | 
| Change in FEV1 | Forced expiratory volume in first second from spirometry | From baseline to completion of study( 7 months total) | 
| Change in FeNO | Exhaled nitric oxide | From baseline to completion of study( 7 months total) | 
| Eosinophil count | Absolute eosinophil count | From baseline to completion of study( 7 months total) | 
| Total serum IgE | Total IgE | From baseline to completion of study( 7 months total) | 
| Serum tryptase | Biomarker | From baseline to completion of study( 7 months total) | 
| Serum TARC (thymus and activation regulated cytokine) | Biomarker | From baseline to completion of study( 7 months total) | 
| Serum prostaglandin D2 | Biomarker | From baseline to completion of study( 7 months total) | 
| 24 hour urinary leukotriene E4 | Biomarker | From baseline to completion of study( 7 months total) | 
| To assess the safety and tolerability of dupilumab | Adverse events | From baseline to completion of study( 7 months total) | 
| To assess cumulative dose of systemic steroids | Impact on systemic steroids | From baseline to completion of study( 7 months total) |