MAIN STUDY: SWITCH SUB-STUDY: SWITCH-JCV
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: teriflunomide
Intervention description: 14 mg oral teriflunomide daily
Intervention MeSH terms: Teriflunomide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 21 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: teriflunomide; natalizumab; relapsing multiple sclerosis

Summary:

      MAIN STUDY: The purpose of this study is to determine if teriflunomide will be safe and
      effective to prevent relapses in patients with relapsing types of MS when switching from
      natalizumab to teriflunomide in patients at risk for PML. This is a two center interventional
      study of patients who have had 12 or more continuous infusions of natalizumab , who are
      anti-JCV-ab positive, and who had been free of clinical relapses during prior 12 months of
      natalizumab therapy who will be switching to teriflunomide.

      SUB-STUDY: To study the number of patients experiencing a reduction in the anti-JCV antibody
      Index value in patients who had received at least one dose of teriflunomide during
      participation in the SWITCH protocol (main study).
    

Eligibility criteria:

        MAIN STUDY

        Inclusion Criteria:

          -  Male and female patients, age 21 to 60 with relapsing forms of MS, treated with
             natalizumab for 12 consecutive months or longer with anti-JCV Ab positive during that
             time period.

          -  Able to understand and sign Informed Consent Document.

          -  Stable disease during treatment with natalizumab. No clinical relapses for at least 12
             months.

          -  Stable MRI on follow-up MRI scans for prior 12 months without evidence of new or
             enlarging T-2 hyperintensities or Gd+ lesions.

          -  No clinical evidence by imaging or cerebrospinal fluid (CSF) for PML.

          -  No evidence of significant cognitive limitation or psychiatric disorder.

          -  Expanded Disability Status Scale (EDSS) of 1.0 to 6.0 inclusive.

        Exclusion Criteria:

          -  Any mental condition of such that patient is unable to understand the nature, scope
             and possible consequences of the study.

          -  Patients that are known HIV positive.

          -  Patients with a known history of hepatitis.

          -  Known history of active tuberculosis not adequately treated, or a positive ppd skin
             test or positive quantiferon gold.

          -  Any persistent or severe infection.

          -  Any malignancy within 5 years, except for Basal or Squamous cell skin lesions, which
             have been surgically excised, with no evidence of metastasis.

          -  Clinically relevant or unstable cardiovascular, neurological (i.e. progressive
             weakness, increasing hypesthesia), endocrine, or other major systemic diseases.

          -  History of drug or alcohol abuse within the past year.

          -  Any significant depression or psychiatric disease (BDI II greater than 25) within the
             past year.

          -  Any significant lab abnormality as deemed by the investigator including but not
             limited to the following:

               1. Hypoproteinemia with serum albumin < 3.0g/dl.

               2. Serum creatinine >133umol/L (or >1.5 mg/dl)

               3. Hematocrit <24% and/or

               4. Absolute white blood cell count < 4,000 cells/mm3 (µl) and/or

               5. Platelet Count <150,000 cells/mm3 (µl) and /or

               6. Absolute neutrophil < 1,500 cells/mm3 (µl)

               7. Liver function impairment or persisting elevations of serum glutamate pyruvate
                  transaminase (SGPT)/ Alanine transaminase (ALT), serum glutamate oxaloacetate
                  transaminase (SGOT)/ aspartate aminotransferase (AST), or direct bilirubin
                  greater than 1.5 fold the upper limit of normal.

          -  Any confounding illness or other diseases of the spine or bone that would impair
             evaluation of the patient or treatment effects.

          -  Any clinical, CSF or MRI evidence for PML.

          -  Prior treatment with immunosuppressive drugs except for past use of intravenous
             steroids to treat MS relapses.

          -  Pregnant or breast feeding women.

          -  Women of childbearing potential not protected by effective contraceptive method of
             birth control and/or are unwilling or unable to be tested for pregnancy.

          -  In the conception of a child during the course of the trial.

          -  Known history of hypersensitivity to teriflunomide or leflunomide.

          -  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.

          -  Prior use within 4 weeks before randomization or concomitant use of phenytoin,
             warfarin, tolbutamide, cholestyramine, or products containing St. John's Wort

        SUB-STUDY

        Eligibility Criteria for JCV sub-study:

          -  Must have been enrolled in the SWITCH protocol and received at least 1 dose of 14mg
             TFM during the study period.

          -  Must be willing to sign written, informed consent for this JCV sub-study and follow
             protocol requirements.