Clinical trial NCT04806737: Teriflunomide vs. Placebo During Gluten Challenge in Celiac Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Celiac Disease
Keywords: Immunotherapy
Gluten challenge
Teriflunomide
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2021-03-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adaptive T cell activation
timeFrame: Blood sample on the 4th day after a 3 day gluten challenge
Secondary outcomes:
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Dept of Gastroenterology
Study officials:
affiliation: Oslo University Hoapital
name: Pål-Dag Line, MD, PhD
role: STUDY_CHAIR
affiliation: Oslo University Hospital
name: Knut EA Lundin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: