Mechanisms of Dupilumab in AERD

Aspirin-exacerbated Respiratory Disease Clinical Trial

Official title:

Mechanisms of Dupilumab in AERD - Effects on Aspirin Hypersensitivity Response, With a Focus on Innate Type 2 Inflammatory Responses

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05031455
• Other study ID #: SHUCSD06242020
• Status: Recruiting
• Phase: Phase 2
• Start date: March 25, 2024
• Est. completion date: February 28, 2026

Study information

• Verified date: April 2024
• Source: Scripps Clinic
• Contact: Andrew White, MD
• Phone: 858-764-9010
• Email: white.andrew[@]scrippshealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aspirin-Exacerbated Respiratory Disease (AERD), although uncommon in the general population, is an important phenotype of severe asthma and nasal polyposis where it occurs in 15% of severe asthmatics, and up to 30% of those with nasal polyposis. An important therapy for AERD is aspirin therapy after desensitization (ADAT). This is an inexpensive and proven therapy to improve the burden of sinus disease in AERD. Aspirin desensitization is the mechanism by which tolerance is induced in AERD patients. This is a 1-2 day outpatient procedure whereby increasing doses of aspirin are administered and the patients invariably experience some degree of hypersensitivity reactions.

It is important to understand the effect of medications on the aspirin desensitization. It is known that the leukotriene modifier medications decrease the severity of the reactions in AERD. Other treatments such as antihistamines and the biologic agent omalizumab might have an effect on either blocking or blunting reactivity in AERD during desensitization.

Dupilumab is a new respiratory biologic approved for atopic dermatitis, eosinophilic asthma and nasal polyposis. As such, it is well situated to be used for many AERD patients whose disease cannot be well controlled. The effect of dupilumab on the aspirin desensitization process and reaction is unknown and is the topic of this investigation.

The primary objective is to determine the effect of dupilumab on reactions during aspirin challenge/desensitization.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: February 28, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects >18 years old with Aspirin-Exacerbated Respiratory Disease

This is diagnosed via either a positive oral aspirin or intranasal ketorolac challenge OR a history of at least two stereotypical hypersensitivity reactions to aspirin leading to nasal-ocular symptom and/or asthmatic symptoms.

• Current treatment with dupilumab at standard asthma/nasal polyposis dosing of 300mg subcutaneously every 2 weeks for a minimum of 12 weeks.

• All subjects will be required to have a known history of nasal polyposis either via imaging, endoscopy, or nasal examination

Exclusion Criteria:

• History of gastrointestinal reactions (severe abdominal pain with or without vomiting) during NSAID triggered events

• Unstable asthma or history of severe reactions during previous desensitization attempts

• inability to take montelukast pretreatment

• history of gastrointestinal bleeding or bleeding disorder

• pregnancy

• previous use of any other respiratory biologic in the past 3 months (omalizumab, tezepelumab, mepolizumab, reslizumab, benralizumab)

• need for systemic corticosteroids to stabilize asthma prior to challenge

• time from sinus surgery <1 month.

Related Conditions & MeSH terms

• Aspirin-exacerbated Respiratory Disease
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

Drug:
• Aspirin Challenge
Dupilumab is a fully human monoclonal antibody that blocks the receptor component for IL-4 and IL-13, which are key drivers of type 2 inflammation. All subjects will be prescribed this at standard 300mg subcutaneous dosing every 2 weeks. The intervention will be the response to aspirin challenge. All 16 subjects will receive dupilumab. All subjects will undergo an aspirin challenge/desensitization procedure. It is estimated that 50% of subjects will have a respiratory reaction to aspirin and 50% will not. There will not be any randomization.

Locations

Country	Name	City	State
United States	Scripps Clini	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
Scripps Clinic	Regeneron Pharmaceuticals, University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of positive challenges to aspirin challenge	Aspirin challenge reactions will be defined as either 1) >15% drop in FEV1 or 2) >25% drop in peak nasal inspiratory flow (PNIF) or 3) >5 point change in composite symptom score.; Spirometry is a standardized measure of airflow obstruction used to define lower airway reaction to aspirin in AERD.; Nasal inspiratory flow rates are measured using an inverted peak flow meter and have been correlated with nasal obstruction occurring during nasal reactions to aspirin in AERD.; Symptom Score - symptoms are a typical part of an aspirin reaction with increase in congestion, itching, cough, and chest tightness.	Aspirin challenge = 6 weeks after starting dupilumab/placebo. Aspirin challenge day = up to 8 hours