A two-year, double-blind, randomized, multicenter, active controlled, study to evaluate the safety and efficacy of fingolimod administered orally once daily versus interferon β-1a i.m. once weekly in pediatric patients with multiple sclerosis with five-year fingolimod Extension Phase

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

Core phase:
1. Male and female patients aged 10-17 years old, inclusive (i.e., have not yet
had their 18th birthday) at randomization.
2. A diagnosis of MS as defined by the revised consensus definition for
pediatric MS (Krupp et al 2013, Polman et al 2011).
3. Central review of the diagnosis of pediatric MS will be required for all
patients prior to randomization.
4. At least one MS relapse/attack during the previous year or two MS relapses
in the previous two years prior to screening, or evidence of one or more Gd
enhancing lesions on MRI within 6 months prior to randomization (including
screening MRI).
5. Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive.,
Extension Phase:
Criterion applies to all patients entering the Extension Phase;
- Patients that originally met Core Phase Inclusion criteria and completed the
Core phase on or off of study drug.

Criterion applies to patient newly recruited to participate in the Extension
Phase:
Younger cohort is defined as the population of pediatric patients fulfilling
any single one or a combination of the following criteria: being 12 or younger
of age, weighing 40 kg or less, or being pre-pubertal (Tanner stage less than 2)
1. 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. Countries that do not have the 0.25mg dose formulation of
fingolimod
approved according to local label, may only enroll patients within the younger
cohort who
have a body weight above 40 kg and be prescribed the 0.5mg dose level according
to
local label.
2. Central review (including initial MRI report) of the diagnosis of pediatric
MS
(Thompson et al 2018) will be required for all newly recruited patients.

Exclusion Criteria

Core and extension phase:
1. Patients with progressive MS.
2. Patients with widespread and symmetric white matter alterations in the
Screening MRI suggestive of other demyelinating disorders (e.g. metabolic
disorders, mitochondrial disorders).
3. Patients meeting the definition of ADEM (Krupp et al 2013); patients meeting
critieria for neuromyelitis optica (Wingerchuk et al 2006) or tested positive
for aquaporin 4 (AQP4) at Screening. Patients who have tested positive for
anti-MOG (applicable for patients enrolling in the new younger cohort in
extension phase)
4. Patients with active systemic bacterial, viral or fungal infections,
including tuberculosis.
5. Patients without acceptable evidence of immunity to varicella-zoster virus,
mumps, measles, rubella, diphteria, tetanus and pertussis at randomization/
first dose in the extension phase.
6. Patients with any severe cardiac disease or significant findings on the
screening ECG.
7. Positive results of screening period testing for serological markers for
hepatitis A, B, C, and E indicating acute or chronic infection.,
Extension phase:
Criteria apply to patients who completed the Core Phase, but prematurely
discontinued study drug;
- Premature discontinuation of the study drug during the Core Phase due to an
adverse event, serious adverse event, laboratory abnormality or conditions
leading to permanent study drug discontinuation due to safety reasons as
described in the protocol.
- Patients with known new events or concomitant medications that would exclude
them from the Core Phase exclusion criteria.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>EDSS, MRI, MS relapses.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Adverse events, Physical examination (including skin examination), sexual<br /><br>development, ophthalmological examination, pulmonology, lab assessments, ECG,<br /><br>Questionnaires.</p><br>