Dupilumab for Aspirin-exacerbated Respiratory Disease

Phase 2

Completed

• Conditions: Aspirin-exacerbated Respiratory Disease
• Interventions: Drug: Dupilumab

• Registration Number: NCT03595488
• Lead Sponsor: Rochester General Hospital

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.

Study Timeline

• Study First Submitted: 2018-06-29
• Study First Submitted QC: 2018-07-11
• Study First Posted: 2018-07-23
• Study Start: 2018-09-05
• Primary Completion: 2019-12-11
• Study Completion: 2019-12-11
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-25
• Last Update Posted: 2020-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Dupilumab	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Total serum IgE	From baseline to completion of study( 7 months total)	Total IgE
Serum tryptase	From baseline to completion of study( 7 months total)	Biomarker
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
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
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
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
24 hour urinary leukotriene E4	From baseline to completion of study( 7 months total)	Biomarker

Trial Locations

Locations (1)

Rochester Regional Health - Allergy/Immunology; 🇺🇸 Rochester, New York, United States