Phase II Study of Teriflunomide as Adjunctive Therapy to Interferon-beta in Subjects With Multiple Sclerosis

A Randomized, Multinational, Double-Blind, Placebo-Controlled, Parallel-Group Design Pilot Study to Estimate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamic Effects of Teriflunomide for 24 Weeks When Added to Treatment With Interferon-beta in Subjects With Multiple Sclerosis.

The primary objective was to estimate the tolerability and safety of 2 doses of teriflunomide administered once daily for 24 weeks, compared with placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of interferon-β [IFN-β].

Secondary objectives were:

• to estimate the effects of the 2 doses of teriflunomide, compared to placebo, in combination with a stable dose of IFN-β on Magnetic Resonance Imaging [MRI] parameters, relapse rate and patient-reported fatigue;
• to perform pharmacokinetic analyses of the 2 doses of teriflunomide in combination with a stable dose of IFN-β.

The study period per participant was approximatively 44 weeks broken down as follows:

• Screening period up to 4 weeks,
• 24-week double-blind treatment period*,
• 16-week post-treatment elimination follow-up period.

'*' participants successfully completing the week 24 visit were offered the opportunity to enter the optional long-term extension study LTS6047 - NCT00811395.

Inclusion Criteria:

• Definite MS diagnosis according to McDonald's criteria;
• Relapsing clinical course, with or without progression;
• Expanded Disability Status Scale [EDSS] less or equal to 5.5 (ambulatory);
• Stable dose of IFN-β for at least 26 weeks prior to the screening visit;
• No onset of MS relapse in the preceding 60 days prior to randomization;
• Clinically stable for 4 weeks prior to randomization.

Exclusion Criteria:

• Other chronic disease of the immune system, liver function impairment or chronic pancreatic disease;
• Pregnant or nursing woman;
• Alcohol or drug abuse;
• Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
• Human immunodeficiency virus [HIV] positive status;
• Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.