ClinicalTrials.gov
ClinicalTrials.gov Menu

Multi-center, Interventional, Phase 3, Randomized, Double-blinded Study of Treatment:Teriflunomide®, in Radiologically Isolated Syndrome (TERIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03122652
Recruitment Status : Recruiting
First Posted : April 21, 2017
Last Update Posted : October 30, 2018
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Teriflunomide 14 MG Oral Tablet [Aubagio] Drug: Placebo Oral Tablet Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-center, Randomized, Double-blinded Study of Teriflunomide® in Radiologically Isolated Syndrome (RIS) The TERIS Study
Actual Study Start Date : September 25, 2018
Estimated Primary Completion Date : September 25, 2019
Estimated Study Completion Date : September 25, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Terifunomide Drug: Teriflunomide 14 MG Oral Tablet [Aubagio]
1 tablet once a day

Placebo Comparator: Placebo Drug: Placebo Oral Tablet
1 tablet once a day




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. New or enlarging T2 lesions [ Time Frame: Week 48 ]
    Number of new or enlarging T2 lesions on MRI

  2. New or enlarging T2 lesions [ Time Frame: Week 96 ]
    Number of new or enlarging T2 lesions on MRI

  3. New contrast enhancing lesions [ Time Frame: Week 48 ]
    New contrast enhancing lesions on MRI

  4. New contrast enhancing lesions [ Time Frame: Week 96 ]
    New contrast enhancing lesions on MRI

  5. New T2-lesion volumes [ Time Frame: Week 48 ]
    New T2-lesion volumes on MRI

  6. New T2-lesion volumes [ Time Frame: Week 96 ]
    New T2-lesion volumes on MRI

  7. Brain atrophy [ Time Frame: Week 96 ]
    Brain atrophy on MRI



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03122652


Contacts
Contact: Cassandre LANDES 492034126 ext 33 landes.c@chu-nice.fr

Locations
France
CHU de Bordeaux Recruiting
Bordeaux, France, 33000
Contact: Bruno BROCHET, MD         
Principal Investigator: Bruno BROCHET, MD         
CHRU de Lille Recruiting
Lille, France, 59000
Contact: Patrick VERMERSCH, MD         
Contact: , MD         
Principal Investigator: Patrick VERMERSCH         
Hospices Civils de Lyon Recruiting
Lyon, France, 69677
Contact: Sandra VUKUSIC, MD         
Principal Investigator: Sandra VUKUSIC, MD         
Sub-Investigator: Françoise DURAND-DUBIEF, MD         
CHRU de Montpellier Recruiting
Montpellier, France, 34000
Contact: Pierre LABAUGE, MD         
Principal Investigator: Pierre LABAUGE, MD         
CHU de Nantes Recruiting
Nantes, France
Contact: Sandrine WIERTLEWSKI         
Principal Investigator: Sandrine WIERTLEWSKI, MD         
CHU de Nice Recruiting
Nice, France, 06000
Contact: Cassandre LANDES    492034126 ext 33    landes.c@chu-nice.fr   
Principal Investigator: Christine LEBRUN-FRENAY, MD, PhD         
CHU de Nîmes Recruiting
Nîmes, France
Contact: Eric THOUVENOT         
Principal Investigator: Eric THOUVENOT, MD         
APHP - Hôpital La Pitié Salpêtrière Recruiting
Paris, France, 75013
Contact: Anne-Caroline PAPEIX, MD         
Principal Investigator: Anne-Caroline PAPEIX, MD         
Sub-Investigator: Céline LOUAPRE, MD         
Sub-Investigator: Elisabeth MAILLART, MD         
CHU de Rennes Recruiting
Rennes, France, 35000
Contact: Emmanuelle LE PAGE, MD         
Principal Investigator: Emmanuelle LE PAGE, MD         
CHU de Strasbourg Recruiting
Strasbourg, France, 67000
Contact: Jérôme DE SEZE, MD         
Principal Investigator: Jérôme DE SEZE, MD         
CHU de Toulouse Active, not recruiting
Toulouse, France, 31000
Germany
University hospital of Charité Not yet recruiting
Berlin, Germany
Contact: Jens WÜRFEL, MD         
Principal Investigator: Jens WÜRFEL, MD         
University Hospital of the Ruhr - University Bochum Not yet recruiting
Bochum, Germany, D-44791
Contact: Carsten LUKAS, MD         
Principal Investigator: Carsten LUKAS, MD         
University of Heidelberg Not yet recruiting
Heidelberg, Germany, 69120
Contact: Brigitte WILDEMANN, MD         
Principal Investigator: Brigitte WILDEMANN, MD         
University Medical Center of the Johannes Gutenberg Not yet recruiting
Mainz, Germany, 55131
Contact: Frauke ZIPP, MD         
Principal Investigator: Frauke ZIPP, MD         
Technische Universität München Not yet recruiting
Munich, Germany, 81675
Contact: Mark MÜHLAU, MD         
Principal Investigator: Mark MÜHLAU, MD         
Switzerland
University Hospital Basel Not yet recruiting
Basel, Switzerland, 4031
Contact: Ludwig Kappos, MD         
Principal Investigator: Ludwig Kappos, MD         
Turkey
Hacettepe University Not yet recruiting
Ankara, Turkey
Contact: Rana Karabudak, MD         
Principal Investigator: Rana Karabudak, MD         
Mustafa Kemal University Active, not recruiting
Antakya, Turkey
Uludag University School of Medicine Active, not recruiting
Bursa, Turkey
Istanbul University Active, not recruiting
Istanbul, Turkey
Kocaeli University School of Medicine Active, not recruiting
Kocaeli, Turkey
Ondokuz Mayis University, Faculty of Medicine Active, not recruiting
Samsun, Turkey
United Kingdom
Queen's Medical Centre Not yet recruiting
Nottingham, United Kingdom
Contact: Nikos Evangelou, MD         
Principal Investigator: Nikos Evangelou, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Genzyme, a Sanofi Company

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT03122652     History of Changes
Other Study ID Numbers: 14-PP-11
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: October 30, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire de Nice:
Radiologically Isolated Syndrome

Additional relevant MeSH terms:
Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases