Teriflunomide vs. Placebo During Gluten Challenge in Celiac Disease

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.

Inclusion criteria

• 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

Exclusion criteria

• 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