Mechanisms of Dupilumab in AERD

NCT05031455 | Completed Phase 2 FDA Drug

• 1 other identifier: SHUCSD06242020
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aspirin-exacerbated Respiratory Disease

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Aspirin Challenge

EXPERIMENTAL

All subjects will undergo a standardized aspirin challenge

Drug: Aspirin Challenge

Interventions

Aspirin Challenge DRUG

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.

Also known as: Dupixent

Aspirin Challenge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Scripps Clinic: lead
• University of California, San Diego: collaborator
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Scripps Clini

San Diego, California, 92130, United States

Location

MeSH Terms

Interventions

dupilumab

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Aspirin Exacerbated Respiratory Disease Clinic

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: September 2, 2021
• Study Start: March 25, 2024
• Primary Completion: April 20, 2026
• Study Completion: April 20, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)