A study on the efficacy and tolerability of a 14-day treatment with teriflunomide 14 mg tablets vs. placebo in subjects with well-controlled coeliac disease undergoing a 3-day gluten challenge

Phase 1

• Conditions: Coeliac disease; MedDRA version: 20.0Level: PTClassification code 10009839Term: Coeliac diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2020-002307-18-NO
• Lead Sponsor: Oslo University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-06
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 15

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 (IgA-TG2 or IgA Endomysium test) and a duodenal biopsy showing villous atrophy graded as Marsh 3a-3c (1, 2).
•Positive gene test for HLA-DQ2.5
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

•Known intolerance to investigational medical product teriflunomide
•Known intolerance to gluten challenge
•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)
•Any other medical condition that in the opinion of the principal investigator makes the individual unsuitable for participation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy and tolerability of a 14 days treatment with teriflunomide in subjects with well controlled-coeliac disease undergoing a 3-day gluten challenge ;Secondary Objective: Not applicable;Primary end point(s): Induction of the activation marker CD38 on gluten reactive T cells in blood detected by HLA-DQ:gluten tetramers 6 days after the initiation of challenge.;Timepoint(s) of evaluation of this end point: 6 days after the initiation of challenge.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Clinical safety of dosing teriflunomide according to the protocol (loading dose for three days, thereafter 11 days with regular dose)<br>•Clinical safety of gluten challenge in the presence and absence of teriflunomide<br>•Pharmacokinetic and pharmacodynamics aspects of the active drug metabolite triflunomide <br>•Induction of gluten specific T cells binding to HLA-DQ:gluten tetramers in peripheral blood 6 days after the initiation of gluten challenge<br>•Induction of Interleukin-2 and other cytokines in serum measured four hours after initiation of gluten challenge<br>•Presence of gluten-specific T cells as detected with HLA-DQ:gluten tetramers and/or T cell receptor sequencing in blood at follow-up visits <br>;Timepoint(s) of evaluation of this end point: Please see above.