Relapsing multiple sclerosis MedDRA version: 14.1 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Novartis Farmaceutica S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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 consensus definition proposed for pediatric MS (Krupp et al 2007, 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
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). 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 according to the 2007 consensus definition for pediatric MS and related disorders (Krupp et al 2007). 5. Patients who have been previously treated with any IFN ß and 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 o High dose intravenous immunoglobulin within 2 months prior to randomization o Natalizumab within 3 months prior to randomization o Immunosuppressive medications, e.g. azathioprine or methotrexate, within 6 months prior to randomization o Rituximab, ofatumumab or ocrelizumab within 2 years prior to randomization o Cladribine, cyclophosphamide or mitoxantrone 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 IgG antibodies. 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 major congenital heart disease 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 heart rate 450 msec in males and >470 msec in females or relevant risk factors for QT prolongation (e.g. hypokalaemia, mypomagnesemia, congenital QT prolongation) o Second degree Mobitz type II or higher AV block 15. Patients with any pulmonary conditions, as determined by the investigator, including severe asthma defined as per the 2010 WHO uniform definition on severe asthma (Bousquet et al 2010). 16. Positive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the efficacy of fingolimod relative to IFN ß-1a in reducing the number of new/newly enlarging T2 (n/neT2) lesions in children/adolescent MS patients aged 10 to less than 18 years treated for up to 24 months. Other secondary objectives • To evaluate the safety of fingolimod relative to IFN ß-1a in children/adolescent MS patients. • To evaluate the effect of fingolimod relative to IFN ß-1a in children/adolescent MS patients on other relapse-related parameters: o Time to first relapse o Proportion of patients relapse-free • To evaluate the effect of fingolimod relative to IFN ß-1a in children/adolescent MS patients on T1 Gd-enhancing lesions on brain MRI. • To study the pharmacokinetics of fingolimod and fingolimod-P in children/adolescent MS patients treated for up to 24 months. • To study the pharmacokinetic/pharmacodynamic relationship for key efficacy and safety outcomes in children/adolescent MS patients treated for up to 24 months.;Main Objective: To evaluate the efficacy of fingolimod relative to intramuscular IFN ß-1a in reducing the frequency of relapses as assessed by the annualized relapse rate in children/adolescent MS patients aged 10 to less than 18 years treated for up to 24 months.;Primary end point(s): To evaluate the efficacy of fingolimod relative to intramuscular interferon B-1a in reducing the frequency of relapses as assess by the annualized relapse rate (ARR) in children/adolescent MS patients aged 10 to less than 18 years treated for up to 24 months.;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the efficacy of fingolimode relative to IFN B-1a in reducing the number of new/newly enlarging T2 (n/ne T2)lesions in children/adolescent MS patients aged 10 to less than 18 years treated for up to 24 months;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Brazil, Canada, Latvia, Lithuania, Mexico, Spain, United States, Venezuela, Bolivarian Republic of
Contacts
Public ContactDepartamento medico (ICRO)
Novartis Farmaceutica S.A.
Outcome results
None listed