Teriflunomide vs. Placebo During Gluten Challenge in Celiac Disease
Primary Purpose
Celiac Disease
Status
Unknown status
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Teriflunomide Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Celiac Disease focused on measuring Immunotherapy, Gluten challenge, Teriflunomide
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
Sites / Locations
- Dept of GastroenterologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
IMP
Placebo
Arm Description
Teriflunomide 14 mg tablets, first 7 days 5 tablets once pr day, thereafter 1 pr day for another 6 days.
Sham tablets
Outcomes
Primary Outcome Measures
Adaptive T cell activation
Expression of CD38 on HLA-DQ:gluten tetramer positive T cells
Secondary Outcome Measures
Full Information
NCT ID
NCT04806737
First Posted
March 16, 2021
Last Updated
April 16, 2021
Sponsor
Oslo University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04806737
Brief Title
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
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 16, 2021 (Actual)
Primary Completion Date
August 15, 2022 (Anticipated)
Study Completion Date
August 15, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Celiac Disease
Keywords
Immunotherapy, Gluten challenge, Teriflunomide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IMP
Arm Type
Active Comparator
Arm Description
Teriflunomide 14 mg tablets, first 7 days 5 tablets once pr day, thereafter 1 pr day for another 6 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Sham tablets
Intervention Type
Drug
Intervention Name(s)
Teriflunomide Oral Tablet
Other Intervention Name(s)
Gluten challenge
Intervention Description
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.
Primary Outcome Measure Information:
Title
Adaptive T cell activation
Description
Expression of CD38 on HLA-DQ:gluten tetramer positive T cells
Time Frame
Blood sample on the 4th day after a 3 day gluten challenge
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Siv Furholm, BSc
Phone
+4747408122
Email
siv.k.b.furholm@medisin.uio.no
First Name & Middle Initial & Last Name or Official Title & Degree
Jorunn Stamnaes, PhD
Phone
+4798655528
Email
jorunn.stamnas@medisin.uio.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pål-Dag Line, MD, PhD
Organizational Affiliation
Oslo University Hoapital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Knut EA Lundin, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept of Gastroenterology
City
Oslo
ZIP/Postal Code
0881
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Knut Erik A Lundin, MD, PhD
Phone
90980325
Email
k.e.a.lundin@medisin.uio.no
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Teriflunomide vs. Placebo During Gluten Challenge in Celiac Disease
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