Prospective Trial Comparing Swallowed Topical Budesonide With Subcutaneous Dupilumab on Esophageal Diameter and Fibrotic Change in Eosinophilic Esophagitis
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- Mayo Clinic
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Esophageal diameter
研究概览
简要总结
The purpose of this study is to compare Eosinophilic Esophagitis treatments Eohilia with Dupixent in their effects on diameter and scarring of the esophagus.
详细描述
Eosinophilic esophagitis (EoE) is a chronic disease mediated by environmental allergens and type 2 immune inflammation which causes significant symptoms, food impactions, and stenosis. EoE is associated with significant esophageal stricturing disease. In particular, the odds of developing fibrostenotic disease in EoE more than double per decade of life, and the longer symptoms are present prior to diagnosis and treatment, the higher the likelihood of esophageal strictures being present.
Dupilumab and budesonide oral suspension are key treatments for EoE. Dupilumab was FDA approved for EoE in 2022 and inhibits IL-4 and IL-13 signaling which mediate type-2 inflammation and may have an anti-fibrotic effect. IL-13 promotes M2 macrophage polarization, and a recent study showed fibrosis was macrophage-dependent in a mouse model of EoE. Swallowed topical steroids have been used off label in patients with EoE for several years with studies showing effects on improvement in esophageal diameter and reduction in esophageal strictures. The budesonide oral suspension was recently FDA approved in 2024. Further study is needed to understand the effect of these treatments on esophageal stenosis and fibrosis as no clinical trials have compared these treatments or their effects on esophageal diameter to date. Barium esophagram and functional lumen imaging probe (FLIP) are important tools used to measure esophageal diameter in EoE. The investigators hypothesize that dupilumab is superior to topical budesonide oral suspension for its effect on esophagram minimum diameter and FLIP distensibility plateau in EoE patients.
• Primary Efficacy Endpoint:
Alternative Hypothesis: There will be a greater increase in minimum esophageal diameter in patients receiving dupilumab compared to budesonide oral suspension at 12 weeks.
• Secondary Efficacy Endpoint(s):
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, aged ≥18 year of age at Mayo Clinic Rochester or Mayo Clinic Scottsdale at time of informed consent
- •Have a documented diagnosis of EoE per standard guidelines
- •Have histologically active EoE (defined as a peak eosinophil count >15 eosinophils per high-power field; eos/hpf)
- •Weight ≥40 kg
- •Ability to take injectable or oral medication and be willing to adhere to the study intervention regimen
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of dupilumab or budesonide suspension administration. Willingness to complete pregnancy tests during study visits and at end of study.
- •For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
- •Subject agrees to maintain a stable diet
- •Subject is willing to receive weekly injections throughout the study
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements
排除标准
- •Inability to provide informed consent
- •Pregnancy or lactation
- •Contraindication to performing upper endoscopy
- •Known allergic reactions to components of dupilumab or budesonide suspension
- •Non-EoE eosinophilic GI diseases (EGIDs) or hypereosinophilic disorders
- •Prior esophageal surgery, coagulopathy or esophageal varices
- •Known achalasia, crohn's disease, ulcerative colitis, celiac disease
- •Child-Pugh Class C liver disease
- •Failed dupilumab
- •Failed swallowed topical budesonide
- •Erosive esophagitis LA B and above found during EGD
- •Use of prednisone within 2 months prior to study enrollment
- •Treatment with biologic therapies for other disease indications
- •Treatment with medium or high potency topical steroids for skin conditions
- •Autoimmune conditions including lupus, rheumatoid arthritis and psoriatic arthritis
- •Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
研究组 & 干预措施
budesonide oral suspension (Eohilia)
2mg twice daily
干预措施: budesonide oral suspension (Drug)
dupilumab (Dupixent)
300 mg weekly injection
干预措施: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT] (Drug)
结局指标
主要结局
Esophageal diameter
时间窗: from enrollment until up to 14 weeks
the minimum esophageal diameter after 12 weeks of treatment.
次要结局
- Distensibility and diameter change(from baseline to end of treatment at 14 weeks)
- EEsAI questionnaire scores(from enrollment to the end of treatment at 12 weeks)
- Endoscopic refernece score (EREFS)(from enrollment up to end of treatment at 12 weeks)
- Eosinophil counts(from enrollment to the end of treatment at 12 weeks)
- Eoe Histologic Scoring system (EoEHSS)(from enrollment to end of treatment at 12 weeks)
- M2 macrophage polarization(from enrollment to end of treatment at 12 weeks)
- Lamina propria remodeling(from enrollment to end of treatment at week 12)
研究者
Diana L. Snyder
Principal Investigator
Mayo Clinic