efficacy, safety and pharmacokinetics of teriflunomide in pediatric patients with relapsing forms of multiple sclerosis

Conditions: Multiple Sclerosis

Summary: primary objective: to assess the effect of teriflunomide in comparison to placebo on disease activity measured by time to first clinical relapse after randomization in children and adolescents 10 to 17 years of age with relapsing forms of multiple sclerosis (ms). secondary objective: * to assess the effect of teriflunomide in comparison to placebo on disease activity/progression measured by brain magnetic resonance imaging (mri) and on cognitive function. * to evaluate the safety and tolerability of teriflunomide in comparison to placebo. * to evaluate the pharmacokinetics (pk) of teriflunomide.

the study duration included a screening period up to 4 weeks, a double-blind treatment period of up to 96 weeks, an open-label period which included the remainder of the initial 96 weeks, where applicable, and a 96-week extension, i.e., up to a maximum of 192 weeks after randomization. there was a follow-up period of 4 weeks for participants discontinuing treatment. within the 96 weeks double-blind treatment period, the first 4 weeks were pk run-in phase in which pk samples (blood samples) were collected from participants and then 4 weeks of analysis (no samples drawn). the pk run-in phase (total 8 weeks) was intended to provide individual pk parameters to allow the dose adjustment to the 14 milligrams (mg) adult-equivalent dose for the rest of the study. participants who experienced a relapse after the pk run-in phase (8 weeks) and confirmed by the relapse adjudication panel and participants who fulfilled mri criteria (high number of new lesions at weeks 36, 48 or 72 compared to previous images) had the option to continue in an open-label teriflunomide treatment arm up to 192 weeks from randomization. an optional additional extension period was available for young participants with teriflunomide until the participants are 18 years old and/or able to switch to commercial product, whichever comes first.

Eligibility criteria:
* participants with relapsing ms were eligible. participants who met the criteria of ms based on mcdonald criteria 2010 and international pediatric multiple sclerosis study group (ipmssg) criteria for pediatric ms, version of 2012 and had: * at least one relapse (or attack) in the 12 months preceding screening or, * at least two relapses (or attack) in the 24 months preceding screening. * less than 18 years of age and greater than or equal to (\>=) 10 years of age at randomization. specific for the russian federation from 18 december 2014 to 26 july 2016, less than or equal to 17 years of age and \>= 13 years of age at randomization. * signed informed consent/assent obtained from participant and participant's legal representative (parents or guardians) according to local regulations. exclusion criteria: * expanded disability status scale score greater than 5.5 at screening or randomization visits. * relapse within 30 days prior to randomization. * treated with: * glatiramer acetate, interferons, or dimethyl fumarate within 1 month prior to randomization. * fingolimod, or intravenous immunoglobulins within 3 months prior to randomization. * natalizumab, other immunosuppressant or immunomodulatory agents such as cyclophosphamide, azathioprine, cyclosporine, methotrexate, mycophenolate, within 6 months prior to randomization. * cladribine or mitoxantrone within 2 years prior to randomization. * treated with alemtuzumab at any time. * history of human immunodeficiency virus infection. * contraindication for mri. * pregnant or breast-feeding females or those who plan to become pregnant during the study. * female participants of child-bearing potential not using highly effective contraceptive method (contraception in both female and male was required). the above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.