Study Design of a Phase 3 Trial Evaluating Teriflunomide in Children and Adolescents with Relapsing Multiple Sclerosis

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). Teriflunomide showed consistent significant positive effects on annualized relapse rate and disability progression in the phase 3 TEMSO (NCT00134563) and TOWER (NCT00751881) studies with a manageable safety profile in adult patients. Studies have not yet been performed in pediatric patients, who represent approximately 5% of MS cases.

Objectives: To report the TERIKIDS study design, a study planned to evaluate the efficacy, safety, and pharmacokinetics (PK) of teriflunomide compared with placebo in pediatric patients with relapsing forms of MS.

Methods: TERIKIDS is a 2-year, phase 3, multicenter, randomized, double-blind, placebo-controlled study to be conducted in patients (target N=165) aged 10–17 years who satisfy McDonald criteria for MS (2010) and International Pediatric Multiple Sclerosis Study Group criteria for pediatric MS (2013). In addition, patients should have ≥1 or ≥2 relapse(s) in the 12 or 24 months preceding randomization, respectively. Patients will be randomized (2:1) to once-daily teriflunomide or placebo for 96 weeks. The teriflunomide dose will correspond to the adult 14 mg dose, after an 8-week titration and adaption process. The primary objective is to evaluate the effect of teriflunomide compared with placebo on disease activity, as measured by time to first clinical relapse after randomization. Secondary outcomes include proportion of patients relapse-free; brain MRI parameters (number of new/newly enlarged T2, T1 gadolinium-enhancing, and new T1-hypointense lesions, volume of T2 and T1-hypointense lesions, and brain atrophy); cognitive function; safety and tolerability of teriflunomide; and PK evaluation of teriflunomide. During the study, it will be possible to switch to open-label teriflunomide in case of a confirmed relapse (after 8 weeks) or if the number of new/enlarged T2-hyperintense lesions is above a predetermined threshold; however, core study treatment will remain blinded.

Results: Results will be reported after completion of the study.

Conclusions: Results from the study will provide important data surrounding the use of teriflunomide in children and adolescent patients with relapsing forms of MS.