A Phase IIa, Double-blind, Randomised, Placebo-controlled Study on the Efficacy and Tolerability of a 14-day Treatment With Teriflunomide vs. Placebo in Subjects With Coeliac Disease Undergoing a 3-day Gluten Challenge
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Adaptive T cell activation
研究概览
简要总结
The investigators will see if the drug teriflunomide (which is in use in other immune disorder (multiple sclerosis)) can inhibit the immune activation in celiac disease patients during a 3 day gluten challenge. This will be measured in a blood sample.
详细描述
This is a controlled, double-blind, randomised, singlecentre, placebo-controlled, phase IIa proof-of-concept study on effects of the drug on activation and efflux of gluten specific T cells using HLA-DQ:gluten tetramers. The study will be conducted with two treatment groups in the form of a 2:1 parallel group comparison and will serve to compare oral treatment with 14 mg/d teriflunomide vs. placebo in subjects with well-controlled coeliac disease undergoing gluten challenge. The screening period will be up to 8 weeks, followed by a 7-day run-in treatment period with a loading dose of teriflunomide followed by a 6 day therapeutic maintenance dose, an initial 4-week treatment-free follow-up period and a 6 month closing follow-up.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged 18-80
- •Willingness to comply with the study procedures and having signed informed, written consent
- •Previous diagnosis of coeliac disease according to established guidelines based on positive serology (Endomysium test, IgA-TG2 and/or IgGDGP) and a duodenal biopsy showing villous atrophy graded as Marsh 3
- •Positive gene test for HLA-DQ2.5
- •Adherence to gluten-free diet
排除标准
- •Known intolerance to ingredients of teriflunomide or placebo tablets
- •Known intolerance to gluten challenge
- •Known intolerance to cholestyramine
- •Duration of gluten free diet shorter than six months
- •Positive serology (IgA-TG2 below upper level of normal) at screening visit
- •Pregnancy or breast-feeding
- •Not willing to comply with proper pregnancy control (in females)
- •Concomitant medication that interferes with immune activation (e.g. steroids, calcineurin inhibitors, biological treatment for inflammatory bowel disease or other immune disorders, further list is given below)
- •Any other medical condition that in the opinion of the principal investigator makes the individual unsuitable for participation
研究组 & 干预措施
IMP
Teriflunomide 14 mg tablets, first 7 days 5 tablets once pr day, thereafter 1 pr day for another 6 days.
干预措施: Teriflunomide Oral Tablet (Drug)
Placebo
Sham tablets
干预措施: Teriflunomide Oral Tablet (Drug)
结局指标
主要结局
Adaptive T cell activation
时间窗: Blood sample on the 4th day after a 3 day gluten challenge
Expression of CD38 on HLA-DQ:gluten tetramer positive T cells
次要结局
未报告次要终点
研究者
Knut E. A. Lundin
Professor, M.D., PhD., Consultant gastroenterologist
Oslo University Hospital