A Study to Evaluate the Safety of Long Term Treatment With Teriflunomide 14 mg Once Daily in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis in a Long-term Extension Period

Study Overview
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Brief Summary
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National, multicenter study: The study consists of 3 periods: A baseline visit to confirm that patient is still in CIS status. All patients will be clinically evaluated for CDMS and an MRI (less than 2 months) will be analyzed to exclude MS patients according to 2010 Mc Donald's criteria. Treatment period with timed evaluations Post-treatment period: 4 weeks, with 2 visits following study drug discontinuation and accelerated elimination procedure. All patients who discontinue the study drug and according to investgator's decision, will perform the accelerated elimination procedure and the post- accelerated elimination visits (at 2 and 4 weeks after the end of treatment (EOT).

Official Title
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A National, Multi-center Study to Evaluate the Safety of Long Term Treatment With Teriflunomide 14 mg Once Daily in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis in a Long-term Extension Period

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Teriflunomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled in TOPIC study and extension of TOPIC study and currently treated in French extension of TOPIC study who did not convert into MS. A baseline MRI scan (performed less than 2 months before baseline Visit ) confirming that patient is still in CIS status. Exclusion Criteria: Contraindication for MRI, 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 Patients with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymphoproliferative disease, or any patient who has received lymphoid irradiation Known history of active tuberculosis not adequately treated Persistent significant or severe infection History of drug or alcohol abuse Patients must not have used Adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 2 weeks prior to inclusion Prior use within 4 weeks before inclusion or concomitant use of cholestyramine Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate Prior or concomitant use of interferons, cytokine therapy, glatiramer acetate or intravenous immunoglobulins Prior or concomitant use of natalizumab (Tysabri®) Pregnant or breast-feeding women 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. Women wishing to become pregnant during the course of the trial Patients with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia Human immunodeficiency virus (HIV) positive patient Persisting elevations (confirmed by retest) of serum amylase or lipase greater than 2-fold the upper limit of normal Known history of chronic pancreatic disease or pancreatitis Liver function impairment or persisting elevations (confirmed by retest) of serum glutamic pyruvic transaminase (SGPT/ALT), serum glutamic oxaloacetic transaminase (SGOT/AST), or direct bilirubin greater than 1.5-fold the upper limit of normal Known history of active hepatitis Hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum albumin < 3.0 g/dL Moderate to severe impairment of renal function, as shown by serum creatinine > 133 μmol/L (or > 1.5 mg/dL)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriflunomide<br>Teriflunomide 14 mg Once Daily | Drug: Teriflunomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event reporting | evaluation of safety and tolerability of teriflunomide 14mg per day | throughout study completion an average of 6 months | 
| Adverse Events That Are Related to Treatment |  | throughout study completion an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion based on MRI | Conversion to definite MS based on MRI data as defined by the demonstration of dissemination of MRI lesions in time (based on the 2010 revised McDonald criteria) within 3 years | throughout study completion an average of 6 months | 
| Conversion based on Clinical evaluation | Conversion to clinically definite MS based on clinical evaluation and annualized relapse rate (ARR), defined as number of relapses per patient-year | throughout study completion an average of 6 months | 
| Conversion based on annualized relapse rate (ARR) | Conversion to clinically definite MS based on clinical evaluation and annualized relapse rate (ARR), defined as number of relapses per patient-year | throughout study completion an average of 6 months | 
| volume of abnormal brain tissue on MRI |  | 3 years | 
| Disability progression defined as a 1.0-point increase in EDSS score | 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 | confirmed after at least 12 weeks | 
| Proportion of disability-free subjects as assessed by the EDSS | Proportion of disability-free subjects as assessed by the EDSS | throughout study completion an average of 1 year | 
| Fatigue Impact Scale | Patient-reported fatigue based on the Fatigue Impact Scale | throughout study completion an average of 1 year | 
| Quality of life using SF-36 |  | throughout study completion an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis