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

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Radiologically Isolated Syndrome Read More

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