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

March 16, 2023 updated by: Centre Hospitalier Universitaire de Nice

Multi-center, Randomized, Double-blinded Study of Teriflunomide® in Radiologically Isolated Syndrome (RIS) The TERIS Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
125

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France, 33000
        • Chu de Bordeaux
      • Caen, France
        • CHU de Caen
      • Clermont-Ferrand, France
        • CHU de Clermont-Ferrand
      • Grenoble, France
        • CHU de Grenoble
      • Lille, France, 59000
        • CHRU de Lille
      • Lyon, France, 69677
        • Hospices Civils de Lyon
      • Montpellier, France, 34000
        • CHRU de Montpellier
      • Nantes, France
        • CHU de Nantes
      • Nice, France, 06000
        • CHU de Nice
      • Nîmes, France
        • CHU de Nîmes
      • Paris, France, 75013
        • APHP - Hôpital La Pitié Salpêtrière
      • Rennes, France, 35000
        • CHU de Rennes
      • Rouen, France
        • CHU de Rouen
      • Strasbourg, France, 67000
        • CHU de Strasbourg
      • Toulouse, France, 31000
        • CHU de Toulouse
  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital Bern
  • Turkey
      • Ankara, Turkey
        • Hacettepe University
      • Antakya, Turkey
        • Mustafa Kemal University
      • Bursa, Turkey
        • Uludag University School of Medicine
      • Istanbul, Turkey
        • Istanbul University
      • Kocaeli, Turkey
        • Kocaeli University School of Medicine
      • Samsun, Turkey
        • Ondokuz Mayis University, Faculty of Medicine
      • İzmir, Turkey, 35100
        • Ege University Medical Faculty

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Males and females of all ages(>18 years and <65 years) meeting 2009 RIS criteria:

    A. The presence of incidentally identified CNS white matter anomalies meeting the following MRI criteria:

    1. Ovoid, well-circumscribed, and homogeneous foci observed with or without involvement of the corpus callosum
    2. T2 hyperintensities measuring ≥3 mm and fulfilling Barkhof criteria (at least three out of four) for dissemination in space
    3. Anomalies not following a clear vascular pattern
    4. Structural neuroimaging abnormalities identified not explained by another disease process B. No historical accounts of remitting clinical symptoms consistent with neurological dysfunction C. The MRI anomalies do not account for clinically apparent impairments in social, occupational, or generalized area of functioning D. The MRI anomalies are not due to the direct physiological effects of substances (recreational drug use, toxic exposure) or a medical condition E. Exclusion of individuals with MRI phenotypes suggestive of leukoaraiosis or extensive white matter changes lacking clear involvement of the corpus callosum F. The CNS MRI anomalies are not better accounted for by another disease process
  2. Identified RIS cases with the initial MRI demonstrating anomalies suggestive of demyelinating disease dated ≥ 2009
  3. Incidental anomalies identified on MRI of the brain or spinal cord with the primary reason for the acquired MRI resulting from an evaluation of a process other than MS
  4. Affiliation to the social security system

  5. Subjects of reproductive potential are eligible only if the following applies:

    • Women of childbearing potential (WOCBP):Must have a negative serum pregnancy test at Visit 1 (Screening) and negative urine pregnancy test at Visit 2 (Baseline);
    • Must be agree to undertake 1 monthly urine pregnancy tests during the study and up to 6 weeks after the first of two tests showing teriflunomide plasma level <0.02 mg/L;
    • Must agree to use reliable methods of contraception from Visit 1 until 6 weeks after the first oft wo tests showing teriflunomide plasma level <0.02 mg/L.

Fertile male subjects participating in the study who are sexually active with WOCBP:

- Must agree to use condom during the treatment period and for an additional 6 weeks after the first oft wo tests showing teriflunomide plasma level <0.02 mg/L.

Exclusion Criteria:

  1. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of summary of product characteristics (SmPC).
  2. Patients with severe hepatic impairment (Child-Pugh class C).
  3. Patients with severe immunodeficiency states, e.g. AIDS.
  4. Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia.
  5. Patients with severe active infection until resolution.
  6. Patients with severe renal impairment undergoing dialysis.
  7. Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.
  8. Lactating or pregnant women
  9. Subjects wishing to parent a child during the study
  10. Incomplete medical history or radiological data
  11. History of remitting clinical symptoms consistent with multiple sclerosis lasting > 24 hours prior to CNS imaging revealing anomalies suggestive of MS
  12. History of paroxysmal symptoms associated with MS (i.e. Lhermitte's or Uhthoff's phenomena)
  13. CNS MRI anomalies are better accounted for by another disease process
  14. The subject is unwilling or unable to comply with the requirements of the study protocol
  15. Exposure to a disease modifying therapy within the past 3 months
  16. Exposure to high-dose glucocorticosteroid treatment within the past 30 days
  17. Vulnerable subject (such as deprived from freedom) as defined in Section 1.61 of International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.)
  18. Participation in another clinical trial of an investigational medicinal product

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo Oral Tablet
1 tablet once a day
Experimental: Terifunomide
Drug: Teriflunomide 14 MG Oral Tablet [Aubagio]
1 tablet once a day

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to the first acute or progressive neurological event resulting from CNS demyelination.
Time Frame: Week 96

Acute neurological event: The development of an acute neurological episode localized to the optic nerve, brainstem, cerebellum, spinal cord, or long sensory or motor tracts, lasting > 24 hours followed by a period of symptom improvement.

Progressive event: The onset of a clinical symptom (e.g. leg weakness) with the temporal profile revealing at least a 12-month progression of neurological deficits.
Week 96

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
New or enlarging T2 lesions
Time Frame: Week 48
Number of new or enlarging T2 lesions on MRI
Week 48
New or enlarging T2 lesions
Time Frame: Week 96
Number of new or enlarging T2 lesions on MRI
Week 96
New contrast enhancing lesions
Time Frame: Week 48
New contrast enhancing lesions on MRI
Week 48
New contrast enhancing lesions
Time Frame: Week 96
New contrast enhancing lesions on MRI
Week 96
New T2-lesion volumes
Time Frame: Week 48
New T2-lesion volumes on MRI
Week 48
New T2-lesion volumes
Time Frame: Week 96
New T2-lesion volumes on MRI
Week 96
Brain atrophy
Time Frame: Week 96
Brain atrophy on MRI
Week 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire de Nice

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Genzyme, a Sanofi Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christine LEBRUN-FRENAY, MD, Centre Hospitalier Universitaire de Nice

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 25, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 5, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 4, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 12, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14-PP-11

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Conditions

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