Mechanisms of Dupilumab in AERD

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

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.

Study Overview

• Status: Completed
• Conditions: Aspirin-exacerbated Respiratory Disease
• Intervention / Treatment: Drug: Aspirin Challenge

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92130
      • Scripps Clini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Aspirin Challenge; All subjects will undergo a standardized aspirin challenge

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.; Other Names: Dupixent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Scripps Clinic
• Collaborators: University of California, San Diego; Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Actual): April 20, 2026
• Study Completion (Actual): April 20, 2026

Study Registration Dates

• First Submitted: August 19, 2021
• First Submitted That Met QC Criteria: August 31, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiration Disorders; Respiratory Tract Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; dupilumab
• Other Study ID Numbers: SHUCSD06242020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes