This double-blind, double-dummy study will evaluate the safety and efficacy of ocrelizumab compared with fingolimod in children and adolescents with RRMS aged between 10 and \< 18 years over a flexible duration. The double-blind period will last until after the last participant randomized has completed 24 weeks.
This Phase III randomized, double-blind, double-dummy, multicenter study will evaluate the safety and efficacy of ocrelizumab administered as intravenous (IV) infusion every 24 weeks (Q24W) compared with fingolimod taken orally (PO), once daily (QD), in children and adolescents with RRMS aged between 10 and \< 18 years. Participants will be randomized in a 1:1 ratio (ocrelizumab:fingolimod), globally. This study consists of a double-blind, double dummy period in which participants will be treated with either active ocrelizumab or active fingolimod for a flexible duration. Participants who complete the double-blind period will be offered the possibility to enter an optional open-label extension (OLE) treatment period of at least 144 weeks with ocrelizumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
188
Ocrelizumab, 300 milligrams (mg) will be administered as IV infusion to participants who weigh \< 35 kilograms (kg), and ocrelizumab 600 mg, IV will be administered to participants who weigh ≥ 35 kg on Days 1 and 15 (half the dose, 2 weeks apart), and Q24W thereafter.
Ocrelizumab matching placebo will be administered as IV infusion on Day 1 and Day 15, and Q24W thereafter.
Fingolimod will be administered QD as a capsule per the prescribing information (0.25 mg to participants who weigh ≤ 40 kg and 0.5 mg to participants who weigh \> 40 kg).
Protocol-defined Annualized Relapse Rate (ARR)
The population-level summary is rate ratio of ARR. The ARR is calculated as the total number of protocol-defined relapses divided by the total patient-years. Protocol-defined relapse is the occurrence of new/worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by relatively stable or improving neurological state for ≥ 30 days. Symptoms must persist for \>24 hours \& should not be attributable to confounding clinical factors. The new/worsening neurological symptoms must be accompanied by objective neurological worsening consistent with an increase of at least half a step on the expanded disability status scale (EDSS) score, or 2 points on one of the appropriate functional system (FS) scores, or 1 point on two or more of the appropriate FS scores. The change must affect the selected FS (i.e., pyramidal, ambulation, cerebellar, brainstem, sensory, or visual). Adjusted values were reported. OM assessed non inferiority of ocrelizumab vs fingolimod.
Time frame: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)
Protocol-defined ARR
The population-level summary is rate ratio of ARR. The ARR is calculated as the total number of protocol-defined relapses divided by the total patient-years. Protocol-defined relapse is the occurrence of new/worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by relatively stable or improving neurological state for ≥ 30 days. Symptoms must persist for \>24 hours \& should not be attributable to confounding clinical factors. The new/worsening neurological symptoms must be accompanied by objective neurological worsening consistent with an increase of at least half a step on the expanded disability status scale (EDSS) score, or 2 points on one of the appropriate functional system (FS) scores, or 1 point on two or more of the appropriate FS scores. The change must affect the selected FS (i.e., pyramidal, ambulation, cerebellar, brainstem, sensory, or visual). Adjusted values were reported. OM assessed non superiority of ocrelizumab vs fingolimod.
Time frame: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)
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Fingolimod matching placebo will be administered QD as a capsule.
UC San Diego
La Jolla, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Hospital
Washington D.C., District of Columbia, United States
Johns Hopkins Medicine
Baltimore, Maryland, United States
Boston Children's Hospital Central Pharmacy
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
Cleveland Clinic, Mellen Center for Multiple Sclerosis
Cleveland, Ohio, United States
The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company
Columbus, Ohio, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, United States
...and 61 more locations
Number of New or Enlarging T2-hyperintense Lesions (T2 Lesions), as Detected by Brain Magnetic Resonance Imaging (MRI)
Number of new or enlarging T2 lesions for each participant was calculated as the sum of the individual number of new or enlarging T2 lesions as detected by brain MRI.
Time frame: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)
Number of T1 Gd Lesions at Week 12
Brain MRI with and without a Gd-contrast agent were performed to assess the number of Gd lesions.
Time frame: At Week 12
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Up to approximately 7 years
Maximum Serum Concentration (Cmax) of Ocrelizumab
Time frame: Cycle (1 Cycle=24 weeks)
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (AUC Tau) of Ocrelizumab
Time frame: Cycle 1 (1 Cycle=24 weeks)
Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab
Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). The total number of participants who developed ADAs to atezolizumab was determined by summing the ADA-positive participants across all timepoints.
Time frame: Up to approximately 7 years
Levels of Cluster of Differentiation 19 (CD19) + B-cell Count in Blood
CD19+ B-cell count in blood will be assessed using flow cytometry.
Time frame: Up to approximately 7 years