NCT03122652: TERIS

Randomized, Double-blinded Study of Treatment:Teriflunomide, in Radiologically Isolated Syndrome

Completed Phase 3 Last updated 17 March 2023

What this trial tests

Phase 3 trial testing Teriflunomide 14 MG Oral Tablet [Aubagio] in Multiple Sclerosis in 125 participants. Completed in 4 October 2022.

Timeline

25 September 2017

Primary endpoint
5 February 2019

4 October 2022

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Nice
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	125
Start date	25 September 2017
Primary completion	5 February 2019
Estimated completion	4 October 2022
Sites	23 locations across France, Switzerland, Turkey (Türkiye)

Drugs / interventions tested

• Teriflunomide 14 MG Oral Tablet [Aubagio] — full drug profile →
• Placebo Oral Tablet — full drug profile →

Conditions studied

• Multiple Sclerosis — all drugs for Multiple Sclerosis →

Sponsor

Centre Hospitalier Universitaire de Nice

Who can join

18 and older, any sex, with Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Multiple sclerosis (MS) is a common cause of severe neurological disability in young adults, resulting from an autoimmune interruption of both myelin and axons within the central nervous system (CNS). The diagnosis is made by fulfilling both spatial criteria, by meeting the requisite number of lesions within the brain or spinal cord, along with criteria for time, by demonstrating a history of at least a second clinical attack or the development of a new MS lesion on MRI after the seminal neurological event. In the case of MS, healthy individuals who do not exhibit signs of neurological dysfunction commonly have brain MRI studies performed for a reason other than an evaluation for MS that reveal unexpected anomalies highly suggestive of demyelinating plaques given their size, location, and morphology. These healthy subjects lack symptomatology suggestive of MS and fulfill formal criteria for radiologically isolated syndrome (RIS), a recently described MS subtype that expands upon the phenotype of at-risk individuals for future demyelinating events. The discovery of such anomalies creates intersecting neuro-ethical, legal, social, and practical medical management quandaries and is, therefore, of both immediate and long-term clinical significance. Despite advancements in the characterization of RIS subjects, and in our understanding of risk factors for initial symptom development, the effect of treatment on such cases remain unclear.

The purpose of this investigation is to systematically study the efficacy of Teriflunomide in those individuals who possess incidental white matter anomalies within the brain and following a MRI study that is performed for a reason other than for the evaluation of MS.

RIS subjects are frequently exposed to disease modifying therapies despite the lack of scientific literature supporting the use of such treatments. Earlier treatment intervention may extend the time to the first acute or progressive clinical event resulting from CNS demyelination and reduce radiological progression. In addition, early treatment may result in more profound effects on reducing disability progression long-term.

The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination.

This study will include RIS subjects from the Europe who fulfill 2009 RIS Criteria.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial.
   Lebrun-Frénay C, Siva A, Sormani MP, Landes-Chateau C, et al · · 2023 · cited 61× · PMID 37603328 · DOI 10.1001/jamaneurol.2023.2815
2. Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome.
   Lebrun-Frénay C, Rollot F, Mondot L, Zephir H, et al · · 2021 · cited 53× · PMID 34633424 · DOI 10.1001/jamanetworkopen.2021.28271
3. The Multiple Sclerosis Prodrome: Evidence to Action.
   Tremlett H, Munger KL, Makhani N. · · 2021 · cited 29× · PMID 35173664 · DOI 10.3389/fneur.2021.761408
4. Biological Markers in Early Multiple Sclerosis: the Paved Way for Radiologically Isolated Syndrome.
   Rival M, Galoppin M, Thouvenot E. · · 2022 · cited 19× · PMID 35572543 · DOI 10.3389/fimmu.2022.866092
5. Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis.
   Amato MP, De Stefano N, Inglese M, Morena E, et al · · 2022 · cited 12× · PMID 35359637 · DOI 10.3389/fneur.2022.787160
6. Prevalence, Severity, and Clinical Management of Brain Incidental Findings in Healthy Young Adults: MRi-Share Cross-Sectional Study.
   Soumaré A, Beguedou N, Laurent A, Brochet B, et al · · 2021 · cited 5× · PMID 34093421 · DOI 10.3389/fneur.2021.675244
7. Teriflunomide and Epstein-Barr virus in a Spanish multiple sclerosis cohort: <i>in vivo</i> antiviral activity and clinical response.
   Domínguez-Mozo MI, González-Suárez I, Villar LM, Costa-Frossard L, et al · · 2023 · cited 4× · PMID 37841253 · DOI 10.3389/fimmu.2023.1248182
8. Multiple sclerosis in 2020: un bon cru.
   Maillart E, Lubetzki C. · · 2021 · cited 1× · PMID 33340473 · DOI 10.1016/s1474-4422(20)30441-5