A Study To Evaluate Safety And Efficacy Of Ocrelizumab In Comparison With Fingolimod In Children And Adolescents With Relapsing-Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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This double-blind, double-dummy study will evaluate the safety and efficacy of ocrelizumab compared with fingolimod in children and adolescents with relapsing-remitting multiple sclerosis aged between 10 and < 18 years over a duration of at least 96 weeks.

Detailed Description
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This Phase III randomized, double-blind, double-dummy, multicenter study will evaluate the safety and efficacy of ocrelizumab administered by IV infusion every 24 weeks compared with fingolimod taken orally daily, in children and adolescents with Multiple Sclerosis aged between 10 and < 18 years. The study plans to enroll 233 patients in a 1:1 randomization (ocrelizumab:fingolimod), globally. This study consists of a double-blind, double dummy period in which patients will be treated with either active ocrelizumab or active fingolimod for at least 96 weeks. Patients who complete the double-blind period will be offered the possibility to enter an optional open-label extension treatment period of at least 144 weeks with ocrelizumab.

Official Title
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A Phase III Multicenter, Randomized, Double-Blind, Double-Dummy Study To Evaluate Safety And Efficacy Of Ocrelizumab In Comparison With Fingolimod In Children And Adolescents With Relapsing-Remitting Multiple Sclerosis

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Ocrelizumab
* Other: Ocrelizumab Placebo
* Drug: Fingolimod
* Other: Fingolimod Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight ≥ 50 kg Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017 EDSS at screening: 0-5.5, inclusive Neurologic stability for ≥ 30 days prior to screening, and between screening and Day 1 At least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of at least one Gd enhancing lesion on MRI within 6 months Exclusion Criteria: Known presence or suspicion of other neurologic disorders that may mimic MS Significant uncontrolled somatic diseases, known active infection or any other significant condition that may preclude patient from participating in the study Patient with severe cardiac disease or significant findings on the screening ECG

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ocrelizumab<br>Participants will receive Ocrelizumab by IV infusion every 24 weeks. The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15 and subsequent doses are given as single infusions of ocrelizumab every 24 weeks. Participants will also receive a placebo of fingolimod (administered as QD capsule). | Drug: Ocrelizumab<br>* Ocrelizumab will be administered at a dose of 600 mg by IV infusion on Day 1 and Day 15 (half the dose, 2 weeks apart) and every 24 weeks thereafter.<br>Other: Fingolimod Placebo<br>* Fingolimod placebo will be administsred daily as a capsule.<br>|
| Active Comparator: Fingolimod<br>Participants will receive Fingolimod PO QD as per the prescribing information provided with fingolimod. Patients will also receive a placebo of ocrelizumab (administered as IV infusions on Days 1 and 15, and every 24 weeks thereafter). | Other: Ocrelizumab Placebo<br>* Ocrelizumab placebo will be administered by IV infusion on day 1 and Day 15 and every 24 weeks thereafter.<br>Drug: Fingolimod<br>* Fingolimod will be administered daily as 0.5 mg capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized relapse rate (ARR) |  | Baseline up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new or enlarging T2-hyperintense lesions (T2 lesions) as detected by brain MRI during the double-blind period |  | Baseline up to approximately 4 years | 
| Number of new or enlarging T2 lesions by Week 96 |  | Baseline up to Week 96 | 
| Annualized relapse rate (ARR) by Week 96 |  | Baseline up to Week 96 | 
| Number of T1 Gd lesions at Week 12 |  | Week 12 | 
| 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) |  | Baseline up to approximately 8 years | 
| Prevalence of ADAs at baseline and incidence of ADAs during the study |  | Baseline up to approximately 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric Multiple Sclerosis, pediatric MS, children MS, children Multiple Sclerosis, pediatric ocrelizumab