A Study To Evaluate Safety And Efficacy Of Ocrelizumab In Comparison With Fingolimod In Children And Adolescents With Relapsing-Remitting Multiple Sclerosis (Operetta 2)

March 13, 2024 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 relapsing-remitting multiple sclerosis aged between 10 and < 18 years over a duration of at least 96 weeks.

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

233

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 Contact

Study Locations

      • Ciudad Autonoma Buenos Aires, Argentina, C1249ABN
        • Recruiting
        • Hospital de Pediatría S.A.M.I.C.- Prof. Dr. Juan P. Garrahan
      • San Miguel, Argentina, T4000AXL
        • Recruiting
        • Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Recruiting
        • Royal Children's Hospital Melbourne - PIN
      • Wien, Austria, 1090
        • Recruiting
        • Medizinische Universität Wien; Univ.Klinik fuer Neurologie
      • Brussel, Belgium, 1020
        • Recruiting
        • Hôpital Universitaire des Enfants Reine Fabiola; porte 10, batiment K
      • Bruxelles, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires St-Luc
      • Gent, Belgium, 9000
        • Recruiting
        • UZ Gent
    • DF
      • Brasilia, DF, Brazil, 70200-730
        • Recruiting
        • L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME
    • PR
      • Curitiba, PR, Brazil, 81210-310
        • Recruiting
        • Instituto de Neurologia de Curitiba
    • RS
      • Caxias do Sul, RS, Brazil, 95070-560
        • Recruiting
        • Universidade de Caxias do Sul - Rio Grande do Sul
      • Porto Alegre, RS, Brazil, 90610-000
        • Recruiting
        • Hospital Sao Lucas - PUCRS
      • Porto Alegre, RS, Brazil, 90430-001
        • Recruiting
        • Nucleo de Pesquisa Clinica do Rio Grande do Sul NPCR
    • SP
      • Sao Paulo, SP, Brazil, 01228-000
        • Recruiting
        • CPQuali Pesquisa Clínica Sao Paulo
      • Sao Paulo, SP, Brazil, 05403-900
        • Recruiting
        • Inst. Da Criança- Faculdade de Medicina Usp; Unidade de Pneumologia
      • Sao Paulo, SP, Brazil, 01228-200
        • Recruiting
        • Intituto PENSI
      • Sofia, Bulgaria, 1797
        • Recruiting
        • Multiprofile Hospital For Active Treatment In Neurology And Psychiatry (MHATNP) ''St. Naum"
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z1
        • Recruiting
        • University of Alberta Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Recruiting
        • Children's Hospital of Eastern Ontario
      • Split, Croatia, 21000
        • Recruiting
        • University Hospital of Split
      • Zagreb, Croatia, 10000
        • Recruiting
        • Children's Hospital Srebrnjak
      • Aarhus N, Denmark, 8200 N
        • Recruiting
        • Aarhus Universitetshospital
      • Glostrup, Denmark, 2600
        • Recruiting
        • Rigshospitalet Glostrup; Neurologisk Klinik
      • Tallinn, Estonia, 11315
        • Recruiting
        • Astra Kliinik
      • Tartu, Estonia, 51014
        • Recruiting
        • Tartu University Hospital
      • Le Kremlin-bicêtre, France, 94275
        • Recruiting
        • Centre Hospitalier Universitaire de Bicêtre
      • Lyon, France, 69394
        • Recruiting
        • Hopital Pierre Wertheimer - Hopital Neurologique; Service de neurologie
      • Montpellier, France, 34295
        • Recruiting
        • CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie
      • Strasbourg, France, 67091
        • Recruiting
        • Hopital de Hautepierre
      • Datteln, Germany, 45711
        • Recruiting
        • Vestische Kinder- und Jugendklinik Datteln
      • Dresden, Germany, 01307
        • Recruiting
        • Universitaetsklinikum Carl Gustav Carus an der TU Dresden
      • Göttingen, Germany, 37075
        • Recruiting
        • Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Kinder-und Jugendmedizin_UMG
      • Muenster, Germany, 48129
        • Recruiting
        • Universitätsklinikum Münster; Klinik für Kinder- und Jugendmedizin
      • Athens, Greece, 115 28
        • Recruiting
        • Hospital Eginition; First Department of Neurology
      • Chaidari, Greece, 124 62
        • Recruiting
        • Attikon University General Hospital
      • Panorama, Greece, 552 36
        • Recruiting
        • Agios Loucas Clinic SA
      • Thessaloniki, Greece, 546 42
        • Withdrawn
        • Hippokration General Hospital; First Department of Pediatrics
      • Budapest, Hungary, 1088
        • Recruiting
        • Semmelweis Egyetem
      • Debrecen, Hungary, 4032
        • Recruiting
        • Debreceni Egyetem Klinikai Központ; Gyermekklinika
    • Delhi
      • New Delhi, Delhi, India, 110029
        • Recruiting
        • All India Institute Of Medical Sciences (AIIMS)
      • New Delhi, Delhi, India, 110070
        • Recruiting
        • Fortis Flight Lieutenant Rajan Dhall Hospital
    • Gujarat
      • Ahmadabad CITY, Gujarat, India, 380054
        • Recruiting
        • Zydus Hospital; Department of Neuro Sciences
    • Haryana
      • Gurugram, Haryana, India, 122001
        • Recruiting
        • Artemis Hospital
    • Karnataka
      • Bangalore North, Karnataka, India, 560022
        • Recruiting
        • Sparsh Super Speciality Hospital
    • Maharashtra
      • Pune, Maharashtra, India, 411004
        • Recruiting
        • Deenanath Mangeshkar Hospital & Research Centre
    • Abruzzo
      • Chieti, Abruzzo, Italy, 66100
        • Recruiting
        • Universita? G. D'Annunzio; Dipartimento di Neuroscienze, Imaging e Scienze Cliniche
    • Campania
      • Napoli, Campania, Italy, 80131
        • Recruiting
        • A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
    • Friuli-Venezia Giulia
      • Trieste, Friuli-Venezia Giulia, Italy, 34137
        • Recruiting
        • IRCCS Materno Infantile Burlo Garofolo - INCIPIT - PIN
    • Lazio
      • Roma, Lazio, Italy, 00189
        • Recruiting
        • A.O. Sant'Andrea; UOC Neurologia, Dip. di Neuroscienze, Salute Mentale e Organi di Senso (NESMOS)
      • Roma, Lazio, Italy, 00165
        • Recruiting
        • Ospedale Pediatrico Bambino Gesù; Divisione di Neurologia
    • Liguria
      • Genova, Liguria, Italy, 16132
        • Recruiting
        • Irccs A.O.U.San Martino Ist; Dinogmi
    • Lombardia
      • Milano, Lombardia, Italy, 20132
        • Recruiting
        • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Sicilia
      • Catania, Sicilia, Italy, 95123
        • Recruiting
        • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
    • Toscana
      • Pisa, Toscana, Italy, 58126
        • Recruiting
        • Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN
      • Riga, Latvia, LV-1004
        • Recruiting
        • Children's Clinical University Hospital
      • Durango, Mexico, 34000
        • Suspended
        • Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
      • Monterrey, Mexico, 64310
        • Recruiting
        • Iecsi S.C.
      • Veracruz, Mexico, 91900
        • Recruiting
        • FAICIC S de R.L. de C.V; FAICIC Clinical Research
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44280
        • Recruiting
        • Hospital Civil Fray Antonio Alcalde
    • Mexico CITY (federal District)
      • Ciudad de México, Mexico CITY (federal District), Mexico, 03600
        • Recruiting
        • Grupo Medico Camino S.C.
      • Mexico City, Mexico CITY (federal District), Mexico, 06700
        • Recruiting
        • Clinstile S.A de C.V.
    • Michoacan
      • Morelia, Michoacan, Mexico, 58260
        • Recruiting
        • Centro de Investigacion Clinica Chapultepec S. A. de C. V.
    • Sinaloa
      • Culiacán, Sinaloa, Mexico, 80020
        • Recruiting
        • Neurociencias Estudios Clinicos S.C.
      • Culiacán Rosales, Sinaloa, Mexico, 80230
        • Recruiting
        • Centro para el Desarrollo de la Medicina y de Asistencia
      • Fez, Morocco, 30050
        • Recruiting
        • Hassan II University Hospital
      • Rabat, Morocco, 10100
        • Recruiting
        • Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites
      • Rabat, Morocco, 10100
        • Recruiting
        • Hospital Militaire Dinstruction Mohammed V de Rabat
      • Rotterdam, Netherlands, 3015 GD
        • Recruiting
        • Erasmus MC
      • ?ód?, Poland, 93-338
        • Recruiting
        • Instytut Centrum Zdrowia Matki Polki; Klinika Neurologii
      • Gda?sk, Poland, 80-952
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne; Klinika Neurologii Rozwojowej
      • Pozna?, Poland, 60-355
        • Recruiting
        • Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
      • Warszawa, Poland, 04-730
        • Recruiting
        • Instytut Pomnik Centrum Zdrowia Dziecka; Klinika Neurologii i Epileptologii
      • Warszawa, Poland, 02-091
        • Recruiting
        • Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego; Klinika Neurologii Dzieciecej
      • Braga, Portugal, 4710-243
        • Recruiting
        • Hospital de Braga
      • Coimbra, Portugal, 3000-602
        • Recruiting
        • Centro Hospitalar e Universitário de Coimbra E.P.E.; Hospital Pediátrico
      • Lisboa, Portugal, 1169-050
        • Recruiting
        • Hospital Santo Antonio dos Capuchos; Servico de Neurologia
      • Lisboa, Portugal, 1649-035
        • Recruiting
        • Centro Hospitalar Lisboa Norte, E.P.E. ? Hospital de Santa Maria; Servicos Farmaceuticos
      • Bucuresti, Romania, 022102
        • Recruiting
        • Victor Gomoiu Clinical Hospital for Children
      • Bucuresti, Romania, 041914
        • Recruiting
        • Prof Dr Alexandru Obregia Clinical Psychiatric Hospital
      • Belgrade, Serbia, 11000
        • Recruiting
        • Clinic for Neurology and Psychiatry for Children and Youth
      • Belgrade, Serbia, 11000
        • Recruiting
        • Mother and Child Health Care Institute of Serbia Dr Vukan Cupic
      • Belgrade, Serbia, 11000
        • Recruiting
        • Childrens University Hospital
      • Kragujevac, Serbia, 34000
        • Recruiting
        • University Clinical Center Kragujevac; Clinic of neurology
      • NIS, Serbia, 18000
        • Recruiting
        • University Clinical Centre of Nis; Clinic of neurology
      • Nova Sad, Serbia, 21000
        • Recruiting
        • Clinical Centre of Vojvodina
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28006
        • Recruiting
        • Hospital Universitario de la Princesa; Servicio de Neurologia
      • Malaga, Spain, 29010
        • Recruiting
        • Hospital Regional Universitario Carlos Haya; Servicio de Neurologia
      • Sevilla, Spain, 41009
        • Recruiting
        • Hospital Universitario Virgen Macarena; Servicio de Neurologia
    • Barcelona
      • Esplugues De Llobregas, Barcelona, Spain, 08950
        • Recruiting
        • Hospital Sant Joan de Déu
    • Vizcaya
      • Barakaldo, Vizcaya, Spain, 48903
        • Recruiting
        • Hospital de Cruces; Servicio de Neurologia
      • Genève, Switzerland, 1205
        • Withdrawn
        • Hôpitaux Universit. de Genève Méd.Neurologie; Unité de Neurologie pédiatrique
      • Zürich, Switzerland, 8032
        • Recruiting
        • Kinderspital Zurich - Eleonorenstiftung
    • Kharkiv Governorate
      • Lviv, Kharkiv Governorate, Ukraine, 79010
        • Active, not recruiting
        • Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
    • Tavria Okruha
      • Dnipropetrovsk, Tavria Okruha, Ukraine, 49100
        • Active, not recruiting
        • KZ "Dnipropetrovska oblasna dytiacha klinichna likarnia" DOR
      • Birmingham, United Kingdom, B4 6NH
        • Withdrawn
        • Birmingham Children's Hospital
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrookes Hospital
      • Edinburgh, United Kingdom, EH51
        • Recruiting
        • Royal Hospital for Children and Young People
      • London, United Kingdom, WC1N 3JH
        • Recruiting
        • Great Ormond Street Hospital For Children; Neurology
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • UC San Diego; ACTRI
      • San Francisco, California, United States, 94117
        • Recruiting
        • University of California San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • Children's National Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University, Pediatric MS and other Demyelinating Disease Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Robert Wood Johnson Medical School
    • New York
      • New York, New York, United States, 10016
        • Withdrawn
        • NYU Langone Medical Center; Laura and Isaac Perlmutter Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic, Mellen Center for Multiple Sclerosis
      • Columbus, Ohio, United States, 43235
        • Recruiting
        • The Boster Center for MS
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • The Children's Hospital of Philadelphia
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine/Texas Children's Hospital
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University Of Virginia Health System

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 ≥ 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

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 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).
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.
Fingolimod placebo will be administsred daily as a capsule.
Active Comparator: Fingolimod
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).
Ocrelizumab placebo will be administered by IV infusion on day 1 and Day 15 and every 24 weeks thereafter.
Fingolimod will be administered daily as 0.5 mg capsule.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Collaborators

PPD

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

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)

February 4, 2022

Primary Completion (Estimated)

July 7, 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)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

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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