E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009839 |
E.1.2 | Term | Coeliac disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | 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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 days after the initiation of challenge. |
|
E.5.2 | Secondary end point(s) |
• Clinical safety of dosing teriflunomide according to the protocol (loading dose for three days, thereafter 11 days with regular dose)
• Clinical safety of gluten challenge in the presence and absence of teriflunomide
• Pharmacokinetic and pharmacodynamics aspects of the active drug metabolite triflunomide
• Induction of gluten specific T cells binding to HLA-DQ:gluten tetramers in peripheral blood 6 days after the initiation of gluten challenge
• Induction of Interleukin-2 and other cytokines in serum measured four hours after initiation of gluten challenge
• 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
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |