Safety and efficacy of fingolimod in pediatric patients with multiple sclerosis

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 190

Inclusion Criteria

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).
- Central review of the diagnosis of pediatric MS will be required for all patients prior to randomization.
4. At least one MS relapse during the previous year or two MS relapses in the previous two years, preceding enrollment to the study.
5. Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive.
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

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 who have detectable antibodies to IFN ß at Screening.
6. 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 prior to randomization
o Immunosuppressive/immunomodulatory medications such as cladribine, cyclophosphamide, mitoxantrone, azathioprine, methotrexate, rituximab, ofatumumab, ocrelizumab, alemtuzumab, teriflunomide or dimethyl fumarate at any time
o The following antiarrhythmic drugs at Screening: Class Ia (e.g. quinidine, disopyramide) or Class III (e.g. amiodarone, sotalol) anti-arrhythmics
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 non-heartrate lowering medicinal products.
7. Patients diagnosed with macular edema during the pre-randomization phase.
8. Patients with active systemic bacterial, viral or fungal infections, including tuberculosis.
9. Patients who have not completed their vaccination schedule based on the local recommendations.
10. Patients who are negative for varicella-zoster virus, mumps, measles, or rubella, diphtheria, tetanus or pertussis IgG antibodies at Screening.
11. Patients who have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within one month prior to randomization.
12. Patients with a history or presence of malignancy.
13. Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
14. 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