Teriflunomide vs. Placebo During Gluten Challenge in Celiac Disease

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

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.

Study Overview

• Status: Recruiting
• Conditions: Celiac Disease
• Intervention / Treatment: Drug: Teriflunomide Oral Tablet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Siv Furholm, BSc; Phone Number: +4747408122; Email: siv.k.b.furholm@medisin.uio.no
• Study Contact Backup: Name: Jorunn Stamnaes, PhD; Phone Number: +4798655528; Email: jorunn.stamnas@medisin.uio.no

Study Locations

• Norway
  • Oslo, Norway, 0881
    • Recruiting
    • Dept of Gastroenterology
    • Contact: Knut Erik A Lundin, MD, PhD; Phone Number: 90980325; Email: k.e.a.lundin@medisin.uio.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Study Chair: Pål-Dag Line, MD, PhD, Oslo University Hoapital; Principal Investigator: Knut EA Lundin, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Anticipated): August 15, 2022
• Study Completion (Anticipated): August 15, 2022

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Immunotherapy; Teriflunomide; Gluten challenge
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Teriflunomide
• Other Study ID Numbers: 2020-002307-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No