Relapsing-remitting Multiple SclerosisPhase 3Operetta 2NCT05123703
A Study to Evaluate Safety and Efficacy of Ocrelizumab in Comparison With Fingolimod in Children and Adolescents With Relapsing-remitting Multiple Sclerosis (RRMS)
A Phase 3 study testing Ocrelizumab and Fingolimod in people with Relapsing-remitting Multiple Sclerosis, run by Hoffmann-La Roche at 71 sites in 25 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 10 to 17 years
- Conditions the study is for
- Relapsing-remitting Multiple Sclerosis
- What is being tested?
- Ocrelizumab and Fingolimod
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 188 participants
- Where
- 71 sitesin 25 countries
- Study dates
- 19 May 2022to 17 Sep 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
- -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
Who cannot join
- 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)
- -Participants who have discontinued the study during the DBP
Trial locations and contacts
71 sites in 25 countries.
71 sites in 25 countries
United States10 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins Medicine
Baltimore, Maryland, 21287
Boston Children's Hospital Central Pharmacy
Boston, Massachusetts, 02115-5724
Cleveland Clinic, Mellen Center for Multiple Sclerosis
Cleveland, Ohio, 44195-0001
The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company
Columbus, Ohio, 43235
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, 77030-2608
UC San Diego
La Jolla, California, 92037-1337
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4319
Washington University
St Louis, Missouri, 63101
Children's National Hospital
Washington D.C., District of Columbia, 20010
Brazil6 sites
L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME
Brasília, Federal District, 70200-730
Instituto de Neurologia de Curitiba
Curitiba, Paraná, 81210-310
Nucleo de Pesquisa Clinica do Rio Grande do Sul NPCR
Porto Alegre, Rio Grande do Sul, 90430-001
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
CPQuali Pesquisa Clínica Sao Paulo
São Paulo, São Paulo, 01228-000
Inst. Da Criança- Faculdade de Medicina Usp
São Paulo, 05403-900
Italy6 sites
Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari
Bari, Apulia, 70124
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
Catania, Sicily, 95123
Universita? G. D'Annunzio
Chieti, Abruzzo, 66100
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, Lombardy, 20133
Ospedale Pediatrico Bambino Gesù
Rome, Lazio, 00165
Azienda Ospedaliera Sant'Andrea
Rome, Lazio, 00189
Mexico6 sites
Neurociencias Estudios Clinicos S.C.
Culiacán, Sinaloa, 80020
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, 44280
Clinstile S.A de C.V.
Mexico City, Mexico CITY (federal District), 06700
Grupo Médico Camino S.C.
Mexico City, Mexico CITY (federal District), 3310
Centro de Investigacion Clinica Chapultepec S. A. de C. V.
Morelia, Michoacán, 58260
FAICIC S de R.L. de C.V
Veracruz, 91900
Spain5 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Sant Joan De Deu
Esplugues de Llobregas, Barcelona, 08950
Hospital Universitario de la Princesa
Madrid, 28006
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Virgen Macarena
Seville, 41009
France4 sites
Hospices Civils de Lyon - Hôpital Pierre Wertheimer
Bron, Rhône, 69003
Centre Hospitalier Universitaire de Bicêtre
Le Kremlin-Bicêtre, 94275
CHRU de Montpellier, Hopital Gui de Chauliac
Montpellier, 34295
Hopital de Hautepierre
Strasbourg, 67091
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gda?sk, 80-952
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, 60-355
Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego
Warsaw, 02-091
Instytut Pomnik Centrum Zdrowia Dziecka
Warsaw, 04-730
Serbia4 sites
Childrens University Hospital
Belgrade, 11000
Clinic for Neurology and Psychiatry for Children and Youth
Belgrade, 11000
Mother and Child Health Care Institute of Serbia Dr Vukan Cupic
Belgrade, 11000
University Clinical Centre of Nis
Niš, 18000
Greece3 sites
Eginitio University General Hospital of Athens
Athens, Attica, 115 28
University General Hospital ''ATTIKON'' - General Hospital of West Attica H AGIA VARVARA
Chaïdári, Attica, 124 62
St. Luke's Hospital
Thessaloniki, 552 36
Portugal3 sites
Hospital de Braga
Braga, 4710-243
ULS de Coimbra, EPE - Hospitais da Universidade de Coimbra
Coimbra, 3000-602
Hospital Santo Antonio dos Capuchos
Lisbon, 1169-050
Canada2 sites
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Estonia2 sites
Astra Kliinik
Tallinn, 11315
Tartu University Hospital
Tartu, 50406
Germany2 sites
Vestische Kinder- und Jugendklinik Datteln
Datteln, 45711
Universitaetsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307
Hungary2 sites
Semmelweis Egyetem
Budapest, 1094
Debreceni Egyetem Klinikai Kozpont
Debrecen, H-4032
Romania2 sites
Victor Gomoiu Clinical Hospital for Children
Bucharest, 022102
Prof Dr Alexandru Obregia Clinical Psychiatric Hospital
Bucharest, 041914
Argentina1 site
Centro de Investigaciones Médicas Tucuman
San Miguel de Tucumán, T4000AXL
Australia1 site
Royal Children's Hospital Melbourne - PIN
Parkville, Victoria, 3052
Switzerland1 site
Universitäts-Kinderspital Zürich - Eleonorenstiftung
Zurich, 8008
Ukraine1 site
Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
Lviv, Kharkiv Governorate, 79010
United Kingdom1 site
Royal Hospital for Children and Young People
Edinburgh, EH51
About this study
Official 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
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.
Read the 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.
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Being tested
- Ocrelizumab, Ocrelizumab Placebo, Fingolimod, Fingolimod Placebo
- Keywords
- pediatric Multiple Sclerosis, pediatric MS, children MS, children Multiple Sclerosis, pediatric ocrelizumab
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OcrelizumabDrug
Also called RO4964913; Ocrevus
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 PlaceboOther
Ocrelizumab matching placebo will be administered as IV infusion on Day 1 and Day 15, and Q24W thereafter.
FingolimodDrug
Also called Gilenya®
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).
Fingolimod PlaceboOther
Fingolimod matching placebo will be administered QD as a capsule.
| Study group | Role | What they receive |
|---|---|---|
| Ocrelizumab | Experimental | 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. Receives: Drug: Ocrelizumab; Other: Fingolimod Placebo |
| Fingolimod | Active comparator | 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. Receives: Other: Ocrelizumab Placebo; Drug: Fingolimod |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)
Secondary outcomes (8)
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.
Measured: 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)
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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 7 years
Maximum Serum Concentration (Cmax) of Ocrelizumab
Measured: Cycle (1 Cycle=24 weeks)
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (AUC Tau) of Ocrelizumab
Measured: 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.
Measured: 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.
Measured: Up to approximately 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2021
- Study start19 May 2022
- Primary completion9 Jun 2025
- Study completion17 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing-remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 188 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05123703
- Sponsor's protocol ID
- WN42086
- Other IDs
- 2020-004128-41, 2023-506516-40-00, 2023
- Acronym
- Operetta 2
- Status last verified
- Jul 2026
- First submitted
- 16 Nov 2021
- Last updated
- 15 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Mar S, Valeriani M, Steinborn B, Schreiner T, Waubant E, Filippi M, Kotulska K, Mazurkiewicz-Beldzinska M, El Azzouzi B, Lin CJ, Shen YA, Kletzl H, Evershed J, Hogea A, Manlius C, Bonati U, Banwell B. Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study. J Neurol. 2025 Jan 15;272(2):137. doi: 10.1007/s00415-024-12879-z.
PubMed 39812825