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NCT Number: NCT05123703

A Study to Evaluate Safety and Efficacy of Ocrelizumab in Comparison With Fingolimod in Children and Adolescents With Relapsing-remitting Multiple Sclerosis (RRMS)

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Relapsing-Remitting Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases

Age range

10 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro de Investigaciones Médicas Tucuman, San Miguel de Tucumán, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Body weight ≥ 25 kg
  • Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric multiple sclerosis (MS), Version 2012, or McDonald criteria 2017
  • Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
  • For all countries except Germany, 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 prior to randomization

Inclusion criteria

for Optional OLE Period:

-Participants in Group A (ocrelizumab in the DBP) and Group B (fingolimod in the DBP) who, in the opinion of the investigator, may benefit from switching to ocrelizumab and who have completed the DBP with study treatment (ocrelizumab/fingolimod), may participate in the OLE period

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 participant from participating in the study
  • Participants with severe cardiac disease or significant findings on the screening electrocardiograph (ECG)

Exclusion criteria

for Optional OLE Period:

-Participants who have discontinued the study during the DBP

Treatment and study plan

Ocrelizumab

Drug

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.

Other names: RO4964913; Ocrevus

Ocrelizumab Placebo

Other

Ocrelizumab matching placebo will be administered as IV infusion on Day 1 and Day 15, and Q24W thereafter.

Fingolimod

Drug

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).

Other names: Gilenya®

Fingolimod Placebo

Other

Fingolimod matching placebo will be administered QD as a capsule.

Primary outcomes

  1. Protocol-defined Annualized Relapse Rate (ARR)

    Time frame: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)

    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.

Secondary outcomes

  1. Protocol-defined ARR

    Time frame: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)

    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.

  2. Number of New or Enlarging T2-hyperintense Lesions (T2 Lesions), as Detected by Brain Magnetic Resonance Imaging (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 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.

  3. Number of T1 Gd Lesions at Week 12

    Time frame: At Week 12

    Brain MRI with and without a Gd-contrast agent were performed to assess the number of Gd lesions.

  4. Number of Participants With Adverse Events (AEs)

    Time frame: Up to approximately 7 years

    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.

  5. Maximum Serum Concentration (Cmax) of Ocrelizumab

    Time frame: Cycle (1 Cycle=24 weeks)

  6. Area Under the Plasma Concentration-time Curve Over a Dosing Interval (AUC Tau) of Ocrelizumab

    Time frame: Cycle 1 (1 Cycle=24 weeks)

  7. Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab

    Time frame: Up to approximately 7 years

    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.

  8. Levels of Cluster of Differentiation 19 (CD19) + B-cell Count in Blood

    Time frame: Up to approximately 7 years

    CD19+ B-cell count in blood will be assessed using flow cytometry.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • PPD Development, LP

Registry information

Official study title

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

Acronym: Operetta 2

Important dates

Study start
2022
Primary completion
2025
Study completion
2029
First posted
Nov 17, 2021
Registry last updated
Jul 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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