Mechanisms of Dupilumab in AERD

NCT ID: NCT05031455

Last Updated: 2024-04-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-25
• Study Completion Date: 2026-02-28

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aspirin Challenge

All subjects will undergo a standardized aspirin challenge

Group Type: EXPERIMENTAL

Aspirin Challenge

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Dupixent

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Scripps Clinic

OTHER

Sponsor Role: lead

Responsible Party

Andrew White

Director, Aspirin Exacerbated Respiratory Disease Clinic

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Scripps Clini

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Andrew White, MD

Role: CONTACT

white.andrew@scrippshealth.org

858-764-9010

Facility Contacts

Andrew White, MD

Role: primary

white.andrew@scrippshealth.org

858-764-9010

Other Identifiers

SHUCSD06242020

Identifier Type: -

Identifier Source: org_study_id