Mechanisms of Dupilumab in AERD - Effects on Aspirin Hypersensitivity Response, With a Focus on Innate Type 2 Inflammatory Responses
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Rate of positive challenges to aspirin challenge
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Aspirin Challenge
All subjects will undergo a standardized aspirin challenge
干预措施: Aspirin Challenge (Drug)
结局指标
主要结局
Rate of positive challenges to aspirin challenge
时间窗: Aspirin challenge = 6 weeks after starting dupilumab/placebo. Aspirin challenge day = up to 8 hours
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.
次要结局
未报告次要终点
研究者
Andrew White
Director, Aspirin Exacerbated Respiratory Disease Clinic
Scripps Clinic