Relapsing multiple sclerosis MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core Phase: 1. Written informed consent/assent 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). - 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. *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 entering the Extension Phase. 1. Patients that originally met Core Phase Inclusion criteria and completed the Core phase on or off of study drug. Criteria applies to patients newly recruited to participate in the Extension Phase. The 'younger cohort' is defined as the population of pediatric patients fulfilling any single one or a combination of the following criteria: being =12 years of age, or weighing =40 kg, or being pre-pubertal (i.e. pubertal status of Tanner stage =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Core & Extension 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 at 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). 5. Patients treated with: • Systemic corticosteroids or adrenocorticotropic hormone (ACTH) in the 30 days prior to Screening MRI scan • High dose intravenous immunoglobulin within 2 months prior to randomization/ first dose in the extension • Natalizumab within 3 months or teriflunomide within 3 ½ months prior to randomization/ first dose in the extension • Immunosuppressive/immunomodulatory medications such as, azathioprine, methotrexate, laquinimod, ofatumumab, ocrelizumab within 6 months prior to randomization/ first dose in the extension • Alemtuzumab, cladribine, cyclophosphamide, mitoxantrone or rituximab at any time • Fingolimod at any time • The following antiarrhythmic drugs at Screening: Class Ia (e.g. quinidine, disopyramide) or Class III (e.g. amiodarone, sotalol) anti-arrhythmics • 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-heart-rate lowering medicinal products. 6. Patients diagnosed with macular edema during the screening period. 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/first dose in the extension (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/ first dose in the extension 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 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 medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Core Phase: 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.;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. ... See the complete list of objectives including the Extension Phase objectives in the protocol.;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: up to 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: up to 24 months | — |
Countries
Australia, Austria, Belarus, Brazil, Bulgaria, Canada, Croatia, Estonia, France, Germany, Italy, Latvia, Lithuania, Mexico, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
SIA Novartis Baltics Lithuanian Branch
Outcome results
None listed