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

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 proposed for pediatric MS (Krupp et al 2013, Polman et al 2011).
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. 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 lesons 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 the 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 entering the Extension Phase.
1. Patients that originally met Core Phase Inclusion criteria and completed the Core phase on or off of study drug.
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 criteria 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 ,5 months prior to randomization
o Immunosuppressive/immunomodulatory medications such as cladribine, cyclophsphaminde, mitoxantrone, azathioprive, methotrexate, rituximab, 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) 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.
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, mumpa, measles, rubella, diphtheria, tetanus and pertussis at rendomization (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 primary treating physician at each site.
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 major congenital heart disease (exept 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