Relapsing-Remitting Multiple Sclerosis MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria • Able to comply with the study protocol, in the investigator's judgment • Age between >10 to =25 kilograms • Children and adolescents must have received all childhood vaccinations as per local and/or national recommendations for childhood vaccination against infectious diseases • Female patients of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 24 weeks after the final dose of ocrelizumab/ocrelizumab placebo and for 2 months after the final dose of fingolimod/fingolimod placebo Inclusion Criteria Related to Pediatric Multiple Sclerosis • Diagnosis of relapsing-remitting multiple sclerosis (RRMS) in accordance with the international pediatric multiple sclerosis study group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017 (or the most current revision of the IPMSSG criteria or McDonald criteria at the time of study start) • Confirmation of the diagnosis of Pediatric RRMS by the Independent Review of Eligibility Committee prior to randomization • Expanded disability status scale (EDSS) at screening: 0-5.5, both inclusive • Neurologic stability for >=30 days prior to screening, and between screening and Day 1 • At least one relapse during the year prior to screening or two relapses in the previous two years prior to screening or evidence of at least one Gd enhancing lesion on MRI within 6 months prior to randomization (including screening MRI) Are the trial subjects under 18? yes Number of subjects for this age range: 233 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: Exclusions Related to General Health • Pregnancy or lactation • Known presence or suspicion of other neurologic disorders that may mimic MS • Aquaporin-4 positive and/or myelin oligodendrocyte glycoprotein antibody positive at screening • Clinical or laboratory findings at first presentation not typically for MS • Abnormal findings in the cerebrospinal fluid at first presentation • Atypical magnetic resonance imaging (MRI) findings • Significant uncontrolled somatic diseases or any other significant condition • Known active bacterial, viral, fungal, mycobacterial infection, or other infection • Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to Day 1 visit or oral anti-infective agents within 2 weeks prior to Day 1 visit • History or known presence of recurrent or chronic infection • Receipt of a live or live-attenuated vaccine within 6 weeks prior to treatment allocation • History or laboratory evidence of clinically significant coagulation disorders • Peripheral venous access that precludes IV administration and venous blood sampling • Inability to complete MRI scan • Teeth braces interfering with MRI acquisition • History of cancer • Currently active or history of alcohol or drug abuse Exclusion Criteria Related to General Health Specific to Fingolimod Treatment • History of symptomatic bradycardia, recurrent syncope, significant QT prolongation. Patients having risk factors for QT prolongation such as hypokalemia or congenital QT prolongation, and uncontrolled hypertension • Patients who in the previous 6 months had myocardial infarction, unstable angina pectoris, stroke/transient ischemic attack, decompensated heart failure, or New York Heart Association Class III/IV heart failure • Patients with severe cardiac arrhythmias • Patients with second-degree Mobitz type II atrioventricular (AV) block or third-degree AV block, sick-sinus syndrome or sinoatrial heart block • Patients with a baseline QTc interval >=500 milliseconds • Presence of macular edema • Presence of any pulmonary conditions, as determined by the investigator • History of any type of epileptic seizure(s) as well as psychogenic non-epileptic seizure(s) during the past 12 months before screening • Patients with chronic liver or biliary disease, acute or chronic pancreatitis Exclusion Criteria Related to Medications • History of a severe allergic or anaphylactic reaction to humanized or murine MAbs or known hypersensitivity to any component of ocrelizumab solution • Contraindications to or intolerance of oral or IV corticosteroids, antihistamines, or antipyretics • Treatment with any investigational agent within 24 weeks of screening or 5 half-lives • Previous treatment with B-cell-targeted therapies • Any previous treatment with alemtuzumab, anti-CD4, cladribine, mitoxantrone, daclizumab, laquinimod, total body irradiation, or bone marrow transplantation • Treatment with cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, or methotrexate within 24 months prior to treatment allocation • Treatment with natalizumab within 12 months prior to randomization • Previous treatment with fingolimod • Treatment with teriflunomide or any other S1P receptor modulator within 24 weeks prior to treatment allocation • Treatment with dimethyl fumarate within 4 weeks prior to treatment allocation • Treatment with intravenous immunoglobulin within 12 weeks prior to treatment allocation • Treatment with plasmapheresi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate non-inferiority of ocrelizumab compared with fingolimod, based on Protocol-defined annualized relapse rate (ARR);Secondary Objective: • To demonstrate non-inferiority of ocrelizumab compared with fingolimod based on the number of new or enlarging T2-hyperintense lesions (T2 lesions) as detected by brain MRI • To demonstrate the superiority of ocrelizumab versus fingolimod based on the number of new or enlarging T2-hyperintense lesions, number of T1 gadolinium lesions and protocol-defined ARR • To evaluate the safety of ocrelizumab administered by intravenous (IV) infusion every 24-weeks compared with fingolimod administered once a day (QD) by mouth (PO) • To assess the pharmacokinetics of ocrelizumab in all children/adolescents enrolled in this study • To assess the pharmacodynamics in all children/adolescents enrolled in this study, as measured by blood B-cell count • To evaluate the immune response to ocrelizumab;Primary end point(s): 1. Protocol-defined annualized relapse rate (ARR) (non-inferiority);Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of new or enlarging T2 lesions as detected by brain MRI during the double-blind period 2. Number of new or enlarging T2 lesions by Week 96 (non-inferiority) 3. Protocol-defined ARR by Week 96 (non-inferiority) 4. Number of T1 gadolinium (Gd) lesions at Week 12 5. Protocol-defined ARR during the double-blind period (superiority) 6. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) 7. Change from baseline in targeted vital signs and clinical significant abnormalities in electrocardiogram (ECG) parameters 8. Change from baseline in targeted clinical laboratory test results 9. Concentrations of ocrelizumab at indicated time points 10. Levels of CD19 B-cell count in blood 11. Prevalence of anti-drug antibodies (ADAs) against ocrelizumab at baseline 12. Incidence of ADAs against ocrelizumab during the study;Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years 2-3. At Week 96 4. At Week 12 5. Up to approximately 2 years 6. Up to 48 weeks from the date of last infusion of ocrelizumab 7-8. Baseline to 48 weeks from the date of last infusion of ocrelizumab 9. Weeks 1, 2, 12, 24, 36, 48, 60, 72, 84 and 96 10. Baseline to 48 weeks from the date of last infusion of ocrelizumab 11. At Baseline (Week -8 to -1) 12. Weeks 1, 24, 48, 72, 96; OLE Period: Day 1 of Dose 1 and of all doses afterword’s; Safety Follow up: 12, 36, 60, 84, 108, 132 weeks from the date of last infusion of ocrelizumab | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Latvia, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed