Safety and efficacy of fingolimod in pediatric patients with multiple sclerosis

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 190

Inclusion Criteria

Core Phase:
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female patients aged 10-17 years old, inclusive (i.e., have not yet had their 18th birthday) at randomization.
3. A diagnosis of MS as defined by the revised consensus definition for pediatric MS (Krupp et al 2013, Polman et al 2011).
4. Central review of the diagnosis of pediatric MS will be required for all patients prior to randomization.
5. 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).
6. Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive.
*Exception: If, in a specific country, use of interferon-ß-1a IM in children below a certain age is included in the Contraindications section of Avonex (interferon-ß-1a IM) local product information, inclusion of such patients is not permitted in that country. E.g. the Russian Avonex product information lists use in children below the age of 12 years as a contraindication.

Fingolimod Extension Phase:
Criterion 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.
Criterion apply 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 190
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Core Phase:
1. Patients with progressive MS.
2. Patients with an active, chronic disease (or stable but treated with
immune therapy) of the immune system other than MS (e.g. Sjögren's
disease, systemic lupus erythematosus) or with a known
immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug
induced immune deficiency) or tested positive for HIV.
3. Patients with widespread and symmetric white matter alterations in
the Screening MRI suggestive of other demyelinating disorders (e.g.
metabolic disorders, mitochondrial disorders).
4. 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.
5. Patients treated with:
o Systemic corticosteroids or adrenocorticotropic hormone (ACTH) in the
30 days prior to Screening MRI scan
o High dose intravenous immunoglobulin within 2 months prior to
randomization
o Natalizumab within 3 months or teriflunomide within 3 ½ months prior
to randomization
o Immunosuppressive/immunomodulatory medications such as
azathioprine, methotrexate, laquinimod, ofatumumab, ocrelizumab
within 6 months prior to randomization
o Alemtuzumab, cladribine, cyclophosphamide, mitoxantrone or
rituximab at any time
o Fingolimod at any time
o The following antiarrhythmic drugs at Screening: Class Ia (e.g.
quinidine, disopyramide) or Class III (e.g. amiodarone, sotalol) antiarrhythmics
o Concurrently treated with heart-rate-lowering drugs at Screening e.g.:
Beta blockers, heart-rate lowering calcium channel blockers (e.g.
verapamil, diltiazem or ivabradine), digoxin, anticholinesteratic agents,
pilocarpine.
Advice from a cardiologist should be sought regarding the switch to nonheartrate
lowering medicinal products.
6. Patients diagnosed with macular edema during the pre-randomization
phase.
7. Patients with active systemic bacterial, viral or fungal infections,
including tuberculosis.
8. Patients without acceptable evidence of immunity to varicella-zoster
virus, mumps, measles, rubella, diphtheria, tetanus and pertussis at
Randomization (See Appendix 3 Guidance on vaccinations for guidance on acceptable evidence of immunity and requirements for serologic testing).
9. Patients who have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within one month prior to randomization.
10. Patients with a history or presence of malignancy.
11. Patients with any medically unstable condition, as assessed by the investigator.
12. Patients with any severe cardiac disease or significant findings on the screening ECG, such as:
o History of symptomatic bradycardia or recurrent syncope
o Known ischaemic heart disease
o History of congenital heart disease (except conditions such as small
patent ductus arteriosus, atrial septal defect, ventricular septal defect,
or an ECG or rhythm abnormality, which have been assessed by a
pediatric cardiologist and considered to be clinically insignificant).
o Cerebrovascular disease
o History of myocardial infarction
o Congestive heart failure
o History of cardiac arrest
o Uncontrolled hypertension despite prescribed medications
o Resting (sitting) heart rate <55 bpm (in patients 12 years or older)
and <60 bpm (in patients below 12 years)
o Severe untreated sleep apnea.
o Sick sinus syndrome or sino-atrial heart block
o QTc interval >450 msec in males and >460 msec in females or relevant
risk factors for QT prolongation (e.g. hy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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