Multiple Sclerosis MedDRA version: 14.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients with a first acute or subacute, well-defined neurological event consistent with demyelination (i.e. optic neuritis confirmed by an ophthalmologist, spinal cord syndrome, brainstem/cerebellar syndromes) 2. Onset of MS symptoms occurring within 90 days of randomization 3. A screening MRI scan (performed at Visit 1) with 2 or more T2 lesions at least 3 mm in diameter that are characteristic of MS (i.e. at least one lesion is periventricular in location or ovoid in shape) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Unable to obtain written informed consent for the study or consent not given for HIV testing (the informed consent process should be complete with full discussion of approved therapies available to the patient. The patient must have been offered these therapies and must choose to join the study instead of accepting therapy outside of the study.) 2. Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study 3. Patient unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and known unlikelihood of completing the study 4. Age 55 years 5. Contraindication for MRI, e.g., presence of pacemaker, metallic implants in high-risk areas 6. Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease or procedure/medication making implementation of the protocol or interpretation of the study results difficult or that would put the patient at risk by participating in the study 7. Patients with a congenital or acquired severe immunodeficiency, a history of cancer , lymphoproliferative disease, or any patient who has received lymphoid irradiation 8. Known history of active tuberculosis not adequately treated 9. Persistent significant or severe infection 10. History of drug or alcohol abuse 11. Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol 12. Patients must not have used Adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 2 weeks prior to randomization 13. Prior use within 4 weeks before randomization cholestyramine 14. Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate 15. Prior or concomitant use of interferons, cytokine therapy, glatiramer acetate or intravenous immunoglobulins 16. Prior or concomitant use of natalizumab (Tysabri®) 17. Prior treatment with teriflunomide, and prior or concomitant use of leflunomide (ARAVA®) or hypersensitivity to any of the other ingredients or excipients of the investigational product. 18. Prior use of any investigational drug in the preceding 6 months 19. Pregnant or breast-feeding women 20. Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy. 21. Patients wishing to parent children during the course of the trial. 22. Patients with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia • Hematocrit <24% and/or • Absolute white blood cell count <4,000 cells/ mm3 (µL) and/or • Platelet count <150,000 cells/ mm3 (µL) and/or • Absolute neutrophil = 1,500 cells/ mm3 (µL) 23. Human immunodeficiency virus (HIV) positive patient 24. Persisting elevations (confirmed by retest) of serum amylase or lipase greater than 2-fold the upper limit of normal 25. Known history of chronic pancreatic disease or pancreatitis 26. Liver function impairment or persisting elevations (confirmed by retest) of serum glutamicpyruvic transaminase (SGPT/ALT), serum glutamic oxaloacetic transaminase (SGOT/AST),or direct bilirubin greater than 1.5-fold the upper limit of normal 27.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the effect of teriflunomide (7and 14 mg/d) compared to placebo for reducing conversion of patients presenting their first clinical episode consistent with MS to clinically definite MS.;Primary end point(s): The primary endpoint is efficacy (conversion to clinically definite MS).;Secondary Objective: To demonstrate effect of teriflunomide (7and 14 mg/d) compared to placebo for: reducing conversion to definite MS by the demonstration of dissemination of MRI lesions in time, reducing annualized relapse rate, reducing MRI variables, including burden of disease (volume of abnormal brain tissue on MRI) and numnber and volume of Gd-enhanced T1 lesion; other data can be obtained from evaluation of MRI scans from the trial for explanatory evaluation, reducing accumulation of disability for at least 12 weeks as measured by EDSS, reducing patient-reported fatigue. To evaluate safety and tolerability of teriflunomide. To evaluate the long-term safety of teriflunomide in the extension period. Optional pharmacogenomic testing. To demonstrate the effect of early teriflunomide treatment (14 mg/day and 7 mg/day) compared to late teriflunomide treatment (placebo to 14 mg/day and placebo to 7 mg/day) for reducing accumulation of disability. ;Timepoint(s) of evaluation of this end point: Baseline- W12- 24-36-48-60-72-84-96 and 108 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Conversion to definite MS based on MRI data as defined by the demonstration of dissemination of MRI lesions in time (based on the revised McDonald criteria, Appendix A) within 2 years. • Annualized relapse rate, defined as number of relapses per patient-year. • Burden of disease (volume of abnormal brain tissue on MRI) at the last visit on treatment and other MRI variables at the last visit on treatment, including number and volume of Gd-enhanced T1 lesions, volume of T2 lesions, volume of T1 hypointense lesions and atrophy. • Time to disability progression (12 weeks), defined as a 1.0-point increase in EDSS score (or 0.5-point increase for baseline EDSS >5.5) confirmed after at least 12 weeks. • Proportion of disability-free subjects as assessed by the EDSS in the 2 years of placebo-controlled period. • Patient-reported fatigue during the placebo-controlled period. • Optional pharmacogenomic testing aims at assessing the association between the main enzyme systems of teriflunomide metabolism and hepatic safety, and other potential associations between gene variations and clinical outcomes. • Long-term evaluation of safety of teriflunomide in extension period. ;Timepoint(s) of evaluation of this end point: Baseline- W12- 24-36-48-60-72-84-96 and 108 | — |
Countries
Australia, Austria, Belarus, Bulgaria, Canada, Chile, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Lithuania, Mexico, Poland, Romania, Russian Federation, Slovakia, Turkey, Ukraine, United Kingdom, United States
Contacts
Public Contactwww.sanofi-aventis.cz
sanofi-aventis, s.r.o.
Outcome results
None listed