Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis

A 2 Year, Double-blind, Randomized, Multicenter, Active-controlled Core Phase to Evaluate Safety & Efficacy of Daily Fingolimod vs Weekly Interferon β-1a im in Pediatric Patients With Multiple Sclerosis and 5 Year Fingolimod Extension Phase

To evaluate the safety and efficacy of fingolimod vs. interferon beta-1a i.m. in pediatric patients with multiple sclerosis (MS)

The study is divided into a Core Phase, which includes the Double-Blind Treatment Period, and an Extension Phase in which all patients will be treated with fingolimod. The Core Phase is a 24-month, double-blind, randomized, active-controlled, parallel-group multicenter study phase to evaluate the efficacy and safety of fingolimod compared to IFN β-1a in children/adolescent patients aged 10-17 years old with MS. The Extension Phase is a 60-month (5 year) study phase for patients who complete the Core Phase of the study and meet all inclusion/exclusion criteria and for patients who will be recruited in the younger cohort to participate in the Extension Phase. The 'younger cohort' refers to the population of pediatric patients fulfilling any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage <2). The recruitment of the younger cohort (up to 25 patients) was requested as a post- approval health authority commitment

Key Inclusion Criteria Core Phase:

• diagnosis of multiple sclerosis
• at least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of Gd enhancing lesions on MRI within 6 months EDSS score of 0 to 5.5, inclusive

Key Exclusion Criteria Core Phase:

• patients with progressive MS
• patients with an active, chronic disease of the immune system other than MS
• patients meeting the definition of ADEM
• patients with severe cardiac disease or significant findings on the screening ECG.
• patients with severe renal insufficiency

Key Inclusion Criteria Extension Phase:

Applies to all patients participating in the Core Phase and then entering the Extension Phase. 1. Patients that originally met Core Phase Inclusion criteria and completed the Core phase on or off of study drug.

Applies to patients newly recruited to participate in the Extension Phase.

• All newly recruited patients' that enroll directly into the Extension Phase must fulfill the local country health authority product label approved for pediatric age group for inclusion criteria.
• Central review (including initial MRI report) of the diagnosis of pediatric MS will be required for all newly recruited patients.

Key Exclusion Criteria Extension Phase:

Applies to patients who completed the Core Phase, but prematurely discontinued study drug.

1. Premature discontinuation of the study drug during the Core Phase due to:

   • an adverse event,
   • serious adverse event,
   • laboratory abnormality
   • other conditions leading to permanent study drug discontinuation due to safety reasons

2. Patients with known new events or concomitant medications (washout periods required prior to Visit 15) that would exclude them from the Core Phase exclusion criteria. Serological or other additional tests will not be required.

Applies to patients newly recruited in the younger cohort to participate in the Extension Phase.

1. All newly recruited patients in the younger cohort that enroll directly into the Extension Phase must fulfill the exclusion criteria for the core phase.