A Study to Evaluate Safety and Efficacy of Ocrelizumab in Comparison With Fingolimod in Children and Adolescents With Relapsing-remitting Multiple Sclerosis (RRMS) (Operetta 2)

July 14, 2026 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

188

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • San Miguel de Tucumán, Argentina, T4000AXL
        • Centro de Investigaciones Médicas Tucuman
  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital Melbourne - PIN
  • Austria
      • Vienna, Austria, 1090
        • Medizinische Universität Wien
  • Belgium
      • Ghent, Belgium, 9000
        • UZ Gent
  • Brazil
      • São Paulo, Brazil, 05403-900
        • Inst. Da Criança- Faculdade de Medicina Usp
    • Federal District
      • Brasília, Federal District, Brazil, 70200-730
        • L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME
    • Paraná
      • Curitiba, Paraná, Brazil, 81210-310
        • Instituto de Neurologia de Curitiba
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Hospital Sao Lucas - PUCRS
      • Porto Alegre, Rio Grande do Sul, Brazil, 90430-001
        • Nucleo de Pesquisa Clinica do Rio Grande do Sul NPCR
    • São Paulo
      • São Paulo, São Paulo, Brazil, 01228-000
        • CPQuali Pesquisa Clínica Sao Paulo
  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children
  • Estonia
      • Tallinn, Estonia, 11315
        • Astra Kliinik
      • Tartu, Estonia, 50406
        • Tartu University Hospital
  • France
      • Le Kremlin-Bicêtre, France, 94275
        • Centre Hospitalier Universitaire de Bicêtre
      • Montpellier, France, 34295
        • CHRU de Montpellier, Hopital Gui de Chauliac
      • Strasbourg, France, 67091
        • Hopital de Hautepierre
    • Rhône
      • Bron, Rhône, France, 69003
        • Hospices Civils de Lyon - Hôpital Pierre Wertheimer
  • Germany
      • Datteln, Germany, 45711
        • Vestische Kinder- und Jugendklinik Datteln
      • Dresden, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus an der TU Dresden
  • Greece
      • Thessaloniki, Greece, 552 36
        • St. Luke's Hospital
    • Attica
      • Athens, Attica, Greece, 115 28
        • Eginitio University General Hospital of Athens
      • Chaïdári, Attica, Greece, 124 62
        • University General Hospital ''ATTIKON'' - General Hospital of West Attica H AGIA VARVARA
  • Hungary
      • Budapest, Hungary, 1094
        • Semmelweis Egyetem
      • Debrecen, Hungary, H-4032
        • Debreceni Egyetem Klinikai Kozpont
  • India
    • Karnataka
      • Bangalore North, Karnataka, India, 560022
        • Sparsh Super Speciality Hospital
  • Italy
    • Abruzzo
      • Chieti, Abruzzo, Italy, 66100
        • Universita? G. D'Annunzio
    • Apulia
      • Bari, Apulia, Italy, 70124
        • Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari
    • Lazio
      • Rome, Lazio, Italy, 00165
        • Ospedale Pediatrico Bambino Gesu
      • Rome, Lazio, Italy, 00189
        • Azienda Ospedaliera Sant'Andrea
    • Lombardy
      • Milan, Lombardy, Italy, 20133
        • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Sicily
      • Catania, Sicily, Italy, 95123
        • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
  • Latvia
      • Riga, Latvia, LV-1004
        • Children's Clinical University Hospital
  • Mexico
      • Veracruz, Mexico, 91900
        • FAICIC S de R.L. de C.V
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44280
        • Hospital Civil Fray Antonio Alcalde
    • Mexico CITY (federal District)
      • Mexico City, Mexico CITY (federal District), Mexico, 06700
        • Clinstile S.A de C.V.
      • Mexico City, Mexico CITY (federal District), Mexico, 3310
        • Grupo Médico Camino S.C.
    • Michoacán
      • Morelia, Michoacán, Mexico, 58260
        • Centro de Investigacion Clinica Chapultepec S. A. de C. V.
    • Sinaloa
      • Culiacán, Sinaloa, Mexico, 80020
        • Neurociencias Estudios Clinicos S.C.
  • Morocco
      • Marrakesh, Morocco, 40000
        • CHU Mohammed VI
  • Poland
      • Gda?sk, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne
      • Późna, Poland, 60-355
        • Uniwersytecki Szpital Kliniczny w Poznaniu
      • Warsaw, Poland, 04-730
        • Instytut Pomnik Centrum Zdrowia Dziecka
      • Warsaw, Poland, 02-091
        • Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego
  • Portugal
      • Braga, Portugal, 4710-243
        • Hospital de Braga
      • Coimbra, Portugal, 3000-602
        • ULS de Coimbra, EPE - Hospitais da Universidade de Coimbra
      • Lisbon, Portugal, 1169-050
        • Hospital Santo Antonio dos Capuchos
  • Romania
      • Bucharest, Romania, 022102
        • Victor Gomoiu Clinical Hospital for Children
      • Bucharest, Romania, 041914
        • Prof Dr Alexandru Obregia Clinical Psychiatric Hospital
  • Serbia
      • Belgrade, Serbia, 11000
        • Clinic for Neurology and Psychiatry for Children and Youth
      • Belgrade, Serbia, 11000
        • Childrens University Hospital
      • Belgrade, Serbia, 11000
        • Mother and Child Health Care Institute of Serbia Dr Vukan Cupic
      • Niš, Serbia, 18000
        • University Clinical Centre of Nis
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28006
        • Hospital Universitario de La Princesa
      • Seville, Spain, 41009
        • Hospital Universitario Virgen Macarena
    • Barcelona
      • Esplugues de Llobregas, Barcelona, Spain, 08950
        • Hospital Sant Joan de Deu
  • Switzerland
      • Zurich, Switzerland, 8008
        • Universitäts-Kinderspital Zürich - Eleonorenstiftung
  • Ukraine
    • Kharkiv Governorate
      • Lviv, Kharkiv Governorate, Ukraine, 79010
        • Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
  • United Kingdom
      • Edinburgh, United Kingdom, EH51
        • Royal Hospital for Children and Young People
  • United States
    • California
      • La Jolla, California, United States, 92037-1337
        • UC San Diego
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Children's National Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02115-5724
        • Boston Children's Hospital Central Pharmacy
    • Missouri
      • St Louis, Missouri, United States, 63101
        • Washington University
    • Ohio
      • Cleveland, Ohio, United States, 44195-0001
        • Cleveland Clinic, Mellen Center for Multiple Sclerosis
      • Columbus, Ohio, United States, 43235
        • The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4319
        • The Children's Hospital of Philadelphia
    • Texas
      • Houston, Texas, United States, 77030-2608
        • Baylor College of Medicine/Texas Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 17 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ocrelizumab
Participants will receive ocrelizumab, as IV infusion Q24W. 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 Q24W. Participants will also receive a placebo of fingolimod administered as QD capsule.
Drug: Ocrelizumab
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
Other: Fingolimod Placebo
Fingolimod matching placebo will be administered QD as a capsule.
Active Comparator: Fingolimod
Participants will receive fingolimod PO, QD as per the prescribing information provided with fingolimod. Participants will also receive a placebo of ocrelizumab administered as IV infusion on Days 1 and 15, and Q24W thereafter.
Other: Ocrelizumab Placebo
Ocrelizumab matching placebo will be administered as IV infusion on Day 1 and Day 15, and Q24W thereafter.
Drug: Fingolimod
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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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-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.
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
Time Frame: At Week 12
Brain MRI with and without a Gd-contrast agent were performed to assess the number of Gd lesions.
At Week 12
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.
Up to approximately 7 years
Maximum Serum Concentration (Cmax) of Ocrelizumab
Time Frame: Cycle (1 Cycle=24 weeks)
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)
Cycle 1 (1 Cycle=24 weeks)
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.
Up to approximately 7 years
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.
Up to approximately 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Collaborators

PPD Development, LP

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2022

Primary Completion (Actual)

June 9, 2025

Study Completion (Estimated)

September 17, 2029

Study Registration Dates

First Submitted

November 16, 2021

First Submitted That Met QC Criteria

November 16, 2021

First Posted (Actual)

November 17, 2021

Study Record Updates

Last Update Posted (Actual)

July 15, 2026

Last Update Submitted That Met QC Criteria

July 14, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WN42086
  • 2020-004128-41 (EudraCT Number)
  • 2023-506516-40-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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