Effect of Dupilumab on ASS Intolerance and Its Mechanisms in Patients With Aspirin-exacerbated Respiratory Disease (AERD)
试验速览
- 阶段
- 4 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximally tolerated aspirin dose level (stages 125mg, 250mg and 500mg)
研究概览
简要总结
To test the efficacy of dupilumab in patients with AERD regarding the intolerance to salicylic acid after 6 months. This will be evaluated by oral drug provocation testing with low dose salicylic acid after 6 months of dupilumab treatment.
Hypothesis:
After 6 months of therapy, patients will tolerate aspirin dose levels as tested with different dosages (125mg, 250mg and 500 mg).
详细描述
30 patients suffering from AERD will be included in this single-center, prospective, explorative study for treatment with dupilumab. Before study initiation, informed consent will be obtained from all subjects. All patients with AERD can be included according to inclusion- and exclusion criteria.
AERD patients who had already obtained a monoclonal antibody for the treatment of asthma or polyps will also be included if at least a wash out period of 5 half -lives or 3 months has passed. The first visit will be performed at screening (day 0, V1/before dupilumab therapy). Clinically significant abnormal laboratory values will be ruled out prior to the first dose.
All patients will be administered subcutaneous doses of dupilumab in a biweekly fashion.
For several reasons comparison with placebo will not be performed:
- All patients included are in urgent need for an effective treatment.
- The only currently available alternative treatment option is a functional endoscopic sinus surgery (FESS). Usually there is a high recurrence rate after surgery.
- All included patients have a long medical history concerning AERD. The rate of a spontaneous improvement or resolution in this patient population is negligible.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Dupilumab treatment group:
- •Signed and dated informed consent has been obtained
- •Age 18 - 70 years
- •Male or female
- •Diagnosed with AERD (nasal polyps, allergic asthma, aspirin intolerance)
- •Chronic rhinosinusitis with nasal polyps (CRSwNP) (according to the European Position Paper on Rhinosinusitis and Nasal Polyps Guidelines)8
- •Documented aspirin intolerance
- •Asthma bronchial diagnosed by a respiratory physician (based on Global -Initiative for Asthma guidelines)9
排除标准
- •Pregnancy
- •Clinically significant abnormal laboratory values and active infection (Tbc, HIV, hepatitis A/B/C)
- •History of malignancy or immunodeficiency
- •Chronic obstructive lung disorders (COPD), other obstructive lung disorders (bronchiolitis)
- •Need for systemic corticosteroid therapy 1 month prior to screening visit Eosinophilic pneumonia and Churg-Strauss Syndrome
研究组 & 干预措施
Dupilumab
All patients will be administered subcutaneous doses of dupilumab in a monthly fashion. Observation period will be 30 minutes after injection
干预措施: Dupilumab (Drug)
结局指标
主要结局
Maximally tolerated aspirin dose level (stages 125mg, 250mg and 500mg)
时间窗: 6 months
Changes in the maximal ASS dose level tolerations (no toleration, 125mg, 250mg and 500mg) at baseline and after 6 months.
次要结局
- Change of allergic asthma (Spirometry)(6 months)
- Change of nasal polyps (TPS)(6 months)
- Change of nasal polyps (SNOT-22)(6 months)
- Percentage of T and B cell subsets in nasal polyp tissues of patients treated with dupilumab as assessed with confocal microscopy(6 months)
- Change of allergic asthma (Asthma control test)(6 months)
研究者
Tamara Quint
Principal investigator
Medical University of Vienna