Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis and Treated With Interferon-beta
Condition: Multiple Sclerosis Relapse
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Teriflunomide; Placebo (for teriflunomide); Interferon-beta (IFN-beta)
Intervention description: Film-coated tablet
Oral administration; Film-coated tablet
Oral administration; Any of the IFN-beta which are approved for marketed use in the country where the patient is enrolled.
Administration according to the package insert.
Intervention MeSH terms: Interferons; Interferon-beta; Teriflunomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 534.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The primary objective was to demonstrate the effect of teriflunomide, in comparison to
      placebo, on frequency of Multiple Sclerosis (MS) relapses in patients with relapsing forms of
      MS who are treated with Interferon-beta (IFN-beta).

      The secondary objectives were:

        -  Assess the effect of teriflunomide, in comparison to placebo, when added to IFN-beta on:

             -  Disease activity as measured by brain Magnetic Resonance Imaging (MRI)

             -  Disability progression

             -  Burden of disease and disease progression as measured by brain MRI

        -  Evaluate the safety and tolerability of teriflunomide when added to IFN-beta therapy

        -  Assess the pharmacokinetics of teriflunomide in use in addition to baseline IFN-beta
           therapy

        -  Assess associations between variations in genes and clinical outcomes (safety and
           efficacy)

        -  Assess other measures of efficacy of teriflunomide such as fatigue and health-related
           quality of life

        -  Assess measures of health economics (hospitalization due to relapse, including the
           length of stay and any admission to intensive care unit)
    

Eligibility criteria:

        Inclusion criteria :

          -  Patient with relapsing forms of MS treated with IFN-beta

          -  Stable dose of IFN-beta (approved brand) for at least 6 months prior to randomization

          -  Disease activity in the 12 months prior to randomization and after first 3 months of
             IFN-beta treatment (defined by at least 1 relapse supported by EDSS or equivalent
             neurological examination, or, at least 1 brain or spinal cord MRI with at least one T1
             gadolinium enhancing lesion)

        Exclusion criteria:

          -  McDonald criteria for MS diagnosis not met at time of screening visit

          -  EDSS score greater than (>) 5.5 at randomization visit

          -  A relapse within 30 days prior randomization

          -  Persistent significant or severe infection

          -  Patients must not have used adrenocorticotrophic hormone or systemic corticosteroids
             for 2 weeks prior to randomization

          -  Prior or concomitant use of cytokine therapy (except baseline interferons), glatiramer
             acetate or intravenous immunoglobulins in the 3 months preceding randomization

          -  Liver function impairment or persisting elevations (confirmed by retest) of alanine
             aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater
             than 2 times the upper limit of normal range (ULN)

          -  Active hepatitis or hepatobiliary disease or known history of severe hepatitis

          -  Pregnant or breast-feeding women or those who were planning to become pregnant during
             the study

          -  Significantly impaired bone marrow function or significant anemia, leukopenia, or
             thrombocytopenia

          -  Human Immunodeficiency Virus (HIV) positive

          -  Known history of active tuberculosis not adequately treated

          -  Prior use within 2 years preceding randomization or concomitant use of cladribine and
             mitoxantrone

          -  Prior use within 6 months preceding randomization or concomitant use of natalizumab,
             or any other immunosuppressive agents such as azathioprine, cyclophosphamide,
             cyclosporine, methotrexate, mycophenolate, or fingolimod

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.