NCT05031455

Mechanisms of Dupilumab in AERD

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Scripps Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2024-03-25
• Primary completion: 2025-12-31
• Completion: 2026-02-28
• First posted: 2021-09-02
• Last updated: 2024-04-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study