Long Term Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses

• Annualized relapse rate (number of relapses per patient-year) [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ] [ Designated as safety issue: No ]
• Change from baseline in Kurtzke Expanded Disability Status Scale (EDSS) score [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ] [ Designated as safety issue: No ]
• Change from baseline in Multiple Sclerosis Functional Composite (MSFC) score [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ] [ Designated as safety issue: No ]
• Burden of disease : Change from baseline in the volume of abnormal brain tissue as measured by brain Magnetic Resonance Image (MRI) [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ] [ Designated as safety issue: No ]
• Change from baseline in Multiple Sclerosis Quality of Life Questionnaire-54 (MSQoL-54) score [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ] [ Designated as safety issue: No ]
• Change from baseline in subject reported fatigue as assessed by the Fatigue Impact Scale (FIS) [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ] [ Designated as safety issue: No ]

The primary objective is to assess the long-term safety of teriflunomide in multiple sclerosis subjects. The secondary objective is to assess the long-term efficacy.

Subjects completing the HMR 1726D/2001 study are given the opportunity to continue or switch to teriflunomide for 528 weeks or until teriflunomide is commercially available in the country where patient lives;

• subjects on Teriflunomide 7 mg or 14 mg continue on the same dose of teriflunomide.
• subjects on placebo are randomized to teriflunomide 7 mg or 14 mg.

The total study period per subject is 532 weeks or until teriflunomide is commercially available in the country where patient lives, broken up as follows:

• Treatment: 528 weeks or until teriflunomide is commercially available in the country where patient lives,
• Post-washout follow-up: 4 weeks after last treatment intake.

• Experimental: Teriflunomide 7 mg
  Intervention: Drug: teriflunomide (HMR1726)
• Experimental: Teriflunomide 14 mg
  Intervention: Drug: teriflunomide (HMR1726)

Inclusion Criteria:

• Satisfactorily completion of HMR1726D/2001 study with respect to safety.
• If female subject, non-childbearing potential or child bearing potential with adequate contraception.
• Consent to practice/maintain adequate means of contraception throughout the study and for 24 months after the discontinuation of treatment.
• Clinically definite Multiple Sclerosis (MS) as established on entry into HMR1726D/2001 study.
• Extended Disability Status Score(EDSS) between 0 and 6 inclusively, when the subject entered HMR1726D/2001 study.
• Magnetic Resonance Imaging (MRI) criteria must continue to support the diagnosis of clinically definite MS.
• Willingness to participate in a long-term safety and efficacy trial.

Exclusion Criteria:

• Subject who did not complete HMR 1726D/2001 study for safety reasons.
• Subject who developed clinically relevant cardiovascular, hepatic, endocrine or other major disease.
• Pregnancy.
• Breast-feeding.
• Wish to parent.
• Likelihood of requiring treatment during the study period with drugs not permitted.
• Disallowed therapies such asw immunomodulators, immunosuppressants.
• Recent history of drug or alcohol abuse.
• Liver function impairment.
• Abnormal mental conditions.