Teriflunomide vs. Placebo During Gluten Challenge in Celiac Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: Teriflunomide Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IMP<br>Teriflunomide 14 mg tablets, first 7 days 5 tablets once pr day, thereafter 1 pr day for another 6 days. | Drug: Teriflunomide Oral Tablet<br>* 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.<br>* Other names: Gluten challenge;|
| Placebo Comparator: Placebo<br>Sham tablets | Drug: Teriflunomide Oral Tablet<br>* 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.<br>* Other names: Gluten challenge;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adaptive T cell activation | Expression of CD38 on HLA-DQ:gluten tetramer positive T cells | Blood sample on the 4th day after a 3 day gluten challenge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Gluten challenge, Teriflunomide