Clinical trial • Phase III • Neurology
OCRELIZUMAB for Relapsing-remitting multiple sclerosis
Phase III trial of OCRELIZUMAB for Relapsing-remitting multiple sclerosis.
Overview
- Trial Therapeutic Area
- Neurology
- Trial Disease
- Relapsing-remitting multiple sclerosis
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody | Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 20-12-2023
- First CTIS Authorization Date
- 07-02-2024
Trial design
Randomised, fingolimod (gilenya) oral capsules; administered po once daily (qd) as per the fingolimod prescribing information; comparator includes matched placebo (double-dummy design).-controlled Phase III trial in Italy, Germany, Spain and others.
- Randomised
- Yes
- Comparator
- Fingolimod (Gilenya) oral capsules; administered PO once daily (QD) as per the fingolimod prescribing information; comparator includes matched placebo (double-dummy design).
- Target Sample Size
- 89
Eligibility
Recruits 89 paediatric patients.
- Vulnerable Population
- Children and adolescents (paediatric population) are included (age range 10 to <18 years). Age-specific assent and consent documents are provided (assent forms for 10-11 and 12-17, parental/ caregiver ICFs, infant health authorization). Separate subject information/consent materials and optional interview information sheets are provided for adolescents and caregivers; parent/guardian consent is required for minors.
Inclusion criteria
- {"criterion_text":"- Age between 10 to <18 years at randomization with Body weight >=25 kilograms\n- At least one relapse during the year prior to screeningAt least one relapse during the year prior to screening or two relapses in the previous two years prior to screening or evidence of at least one Gd enhancing lesion on MRI within 6 months prior to randomization (including screening MRI) For Germany, the criterion is as follows: Highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy, or patients with rapidly evolving severe RRMS defined by 2 or more disabling relapses in one year, and with at least one Gadolinium enhancing lesion on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI or two relapses in the previous two years prior to screening or evidence of at least one Gd enhancing lesion on MRI within 6 months prior to randomization (including screening MRI) For Germany, the criterion is as follows: Highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy, or patients with rapidly evolving severe RRMS defined by 2 or more disabling relapses in one year, and with at least one Gadolinium enhancing lesion on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI\n- Diagnosis of relapsing-remitting multiple sclerosis (RRMS) in accordance with the international pediatric multiple sclerosis study group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017 (or the most current revision of the IPMSSG criteria or McDonald criteria at the time of study start) and confirmed by the Independent Pediatric MS Review Committee prior to randomization\n- Children and adolescents must have received all childhood vaccinations as per local and/or national recommendations for childhood vaccination against infectious diseases\n- Expanded disability status scale (EDSS) at screening: 0-5.5, both inclusive\n- Female patients of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 24 weeks after the final dose of ocrelizumab/ocrelizumab placebo and for 2 months after the final dose of fingolimod/fingolimod placebo"}
Exclusion criteria
- {"criterion_text":"- Aquaporin-4 positive and/or myelin oligodendrocyte glycoprotein antibody positive\n- Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to Day 1 visit or oral anti-infective agents within 2 weeks prior to Day 1 visit or History or known presence of recurrent or chronic infection\n- Receipt of any type of vaccine (e.g., live or live-attenuated vaccine, non-live) within 6 weeks prior to treatment allocation\n- History of symptomatic bradycardia, recurrent syncope, significant QT prolongation, Patients with severe cardiac arrhythmias\n- Exclusion criteria related to prior treatments for MS, as per protocol\n- Exclusion Criteria Related to Laboratory Findings, as per protocol"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Protocol-defined annualized relapse rate (ARR) (non-inferiority)","definition_or_measurement_approach":"Protocol-defined annualized relapse rate (ARR) (as specified in the protocol)"}
Secondary endpoints
- {"endpoint_text":"- 1. Number of new or enlarging T2 lesions as detected by brain MRI during the double-blind period\n- 2. Number of T1 gadolinium (Gd) lesions at Week 12\n- 3. Protocol-defined ARR during the double-blind period (superiority)\n- 4. 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)\n- 5. Change from baseline in targeted vital signs and clinical significant abnormalities in electrocardiogram (ECG) parameters\n- 6. Change from baseline in targeted clinical laboratory test results\n- 7. Concentrations of ocrelizumab at indicated time points\n- 8. Levels of CD19 B-cell count in blood\n- 9. Prevalence of anti-drug antibodies (ADAs) against ocrelizumab at baseline\n- 10. Incidence of ADAs against ocrelizumab during the study","definition_or_measurement_approach":"Endpoints are measured as described in the protocol: MRI-detected lesion counts by brain MRI (T2 and T1 Gd), ARR as protocol-defined, safety by incidence and NCI CTCAE v5.0 grading, laboratory and vital sign changes measured against baseline, ocrelizumab concentrations at specified time points, CD19 B-cell counts in blood, and ADA prevalence/incidence measured by immunoassay."}
Recruitment
- Planned Sample Size
- 89
- Recruitment Window Months
- 89
- Consent Approach
- Age‑appropriate assent and consent processes: parental/ caregiver informed consent required for minors; assent forms for children/adolescents (separate documents for 10-11 and 12-17); country-specific ICF/assent translations and additional authorization forms (infant health authorization) available. Optional interview information sheets and caregiver/adolescent-specific materials are provided; mobile nursing and site-specific MRI qualification ICFs are included where relevant.
Methods
- Patient recruitment duties assigned to Axon Communications Inc. (listed as 'Patient Recruitment').
- Patient reimbursement and travel arrangements managed via Greenphire LLC (ClinCard / ConneX tools referenced in recruitment documents).
- Global CRO oversight indicated (PPD Global Limited listed as 'Global CRO').
- Country-specific recruitment arrangements/addenda referenced (e.g., 'Addendum-to-Recruitment-Arrangements_DE_Public' for Germany).
Geography
- Total Number Of Sites
- 29
- Total Number Of Participants
- 72
Italy
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 14-04-2026
- Processing Time Days
- 817
- Number Of Sites
- 6
- Number Of Participants
- 10
Sites
- Site Name
- University Hospital Consorziale Policlinico
- Department Name
- U.O. Neurologia Universitaria
- Principal Investigator Name
- Pietro Iaffaldano
- Principal Investigator Email
- pietro.iaffaldano@uniba.it
- Contact Person Name
- Pietro Iaffaldano
- Contact Person Email
- pietro.iaffaldano@uniba.it
- Site Name
- Ospedale Pediatrico Bambino Gesu'
- Department Name
- U.O. Degenza Neurologica
- Principal Investigator Name
- Massimiliano Valeriani
- Principal Investigator Email
- massimiliano.valeriani@opbg.net
- Contact Person Name
- Massimiliano Valeriani
- Contact Person Email
- massimiliano.valeriani@opbg.net
- Site Name
- Università degli Studi "Gabriele d'Annunzio" - Center for Advanced Studies and Technology (CAST)
- Department Name
- Center for Advanced Studies and Technology (CAST)
- Principal Investigator Name
- Valentina Tomassini
- Principal Investigator Email
- valentina.tomassini@unich.it
- Contact Person Name
- Valentina Tomassini
- Contact Person Email
- valentina.tomassini@unich.it
- Site Name
- Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
- Department Name
- Clinica Neurologica
- Principal Investigator Name
- Francesco Patti
- Principal Investigator Email
- patti@unict.it
- Contact Person Name
- Francesco Patti
- Contact Person Email
- patti@unict.it
- Site Name
- IRCCS Foundation Istituto Neurologico Carlo Besta
- Department Name
- Neuroimmunologia e Malattie Neuromuscolari
- Principal Investigator Name
- Valentina Liliana Torri Clerici
- Principal Investigator Email
- Valentina.Torri@istituto-besta.it
- Contact Person Name
- Valentina Liliana Torri Clerici
- Contact Person Email
- Valentina.Torri@istituto-besta.it
- Site Name
- Azienda Ospedaliero-Universitaria Sant Andre
- Department Name
- U.O.C. Neurologia
- Principal Investigator Name
- Giovanni Ristori
- Principal Investigator Email
- giovanni.ristori@uniroma1.it
- Contact Person Name
- Giovanni Ristori
- Contact Person Email
- giovanni.ristori@uniroma1.it
Germany
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 14-04-2026
- Processing Time Days
- 817
- Number Of Sites
- 2
- Number Of Participants
- 1
Sites
- Site Name
- Vestische Kinder- und Jugendklinik Datteln
- Department Name
- Vestische Kinder- und Jugendklinik Datteln Neuropädiatrie
- Principal Investigator Name
- Kevin Rostásy
- Principal Investigator Email
- k.rostasy@kinderklinik-datteln.de
- Contact Person Name
- Kevin Rostásy
- Contact Person Email
- k.rostasy@kinderklinik-datteln.de
- Site Name
- Technische Universitat Dresden
- Department Name
- Universitätsklinikum Carl Gustav Carus an der TU Dresden MS Zentrum/Neurologie Abteilung
- Principal Investigator Name
- Tjalf Ziemssen
- Principal Investigator Email
- tjalf.ziemssen@uniklinikum-dresden.de
- Contact Person Name
- Tjalf Ziemssen
- Contact Person Email
- tjalf.ziemssen@uniklinikum-dresden.de
Spain
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 17-04-2026
- Processing Time Days
- 820
- Number Of Sites
- 4
- Number Of Participants
- 11
Sites
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Neurology
- Principal Investigator Name
- Sara Eichau
- Principal Investigator Email
- saraeichau@gmail.com
- Contact Person Name
- Sara Eichau
- Contact Person Email
- saraeichau@gmail.com
- Site Name
- Sant Joan De Deu Barcelona Hospital
- Department Name
- Neurology
- Principal Investigator Name
- Thais Armangue Salvador
- Principal Investigator Email
- thais.armangue@sjd.es
- Contact Person Name
- Thais Armangue Salvador
- Contact Person Email
- thais.armangue@sjd.es
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Neurology
- Principal Investigator Name
- Lucienne Costa-Frossard França
- Principal Investigator Email
- lufrossard@yahoo.es
- Contact Person Name
- Lucienne Costa-Frossard França
- Contact Person Email
- lufrossard@yahoo.es
- Site Name
- Hospital Universitario De La Princesa
- Department Name
- Neurology
- Principal Investigator Name
- Virginia Meca Lallana
- Principal Investigator Email
- virmeca@hotmail.com
- Contact Person Name
- Virginia Meca Lallana
- Contact Person Email
- virmeca@hotmail.com
France
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 20-04-2026
- Processing Time Days
- 823
- Number Of Sites
- 4
- Number Of Participants
- 20
Sites
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Service de Neurologie
- Principal Investigator Name
- Jerome De Seze
- Principal Investigator Email
- jerome.DESEZE@chru-strasbourg.fr
- Contact Person Name
- Jerome De Seze
- Contact Person Email
- jerome.DESEZE@chru-strasbourg.fr
- Site Name
- Hospital Pierre Wertheimer
- Department Name
- Service de Neurologie
- Principal Investigator Name
- Romain Marignier
- Principal Investigator Email
- romain.marignier@chu-lyon.fr
- Contact Person Name
- Romain Marignier
- Contact Person Email
- romain.marignier@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Service de Neuropédiatrie-Pédiatrie Spécialisée
- Principal Investigator Name
- Pierre Meyer
- Principal Investigator Email
- p-meyer@chu-monpellier.fr
- Contact Person Name
- Pierre Meyer
- Contact Person Email
- p-meyer@chu-monpellier.fr
- Site Name
- Bicetre Hospital
- Department Name
- Service de Neurologie Pédiatrique
- Principal Investigator Name
- Kumaran Deiva
- Principal Investigator Email
- kumaran.deiva@aphp.fr
- Contact Person Name
- Kumaran Deiva
- Contact Person Email
- kumaran.deiva@aphp.fr
Portugal
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 14-04-2026
- Processing Time Days
- 817
- Number Of Sites
- 3
- Number Of Participants
- 2
Sites
- Site Name
- Unidade Local De Saude De Sao Jose E.P.E.
- Department Name
- Paediatric Neurology
- Principal Investigator Name
- Rita Silva
- Principal Investigator Email
- rita.silva@chlc.min-saude.pt
- Contact Person Name
- Rita Silva
- Contact Person Email
- rita.silva@chlc.min-saude.pt
- Site Name
- Unidade Local De Saude De Coimbra E.P.E.
- Department Name
- Center of Child Development – Neuropediatrics
- Principal Investigator Name
- Filipe Palavra
- Principal Investigator Email
- filipepalavra@gmail.com
- Contact Person Name
- Filipe Palavra
- Contact Person Email
- filipepalavra@gmail.com
- Site Name
- CCAB Centro Clinico Academico Braga Associacao
- Department Name
- Neurology Department
- Principal Investigator Name
- João Cerqueira
- Principal Investigator Email
- jcerqueira@med.uminho.pt
- Contact Person Name
- João Cerqueira
- Contact Person Email
- jcerqueira@med.uminho.pt
Poland
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 16-04-2026
- Processing Time Days
- 819
- Number Of Sites
- 4
- Number Of Participants
- 18
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny W Poznaniu
- Department Name
- Oddział Kliniczny Neurologii Dzieci i Młodzieży
- Principal Investigator Name
- Barbara Steinborn
- Principal Investigator Email
- bstein@ump.edu.pl
- Contact Person Name
- Barbara Steinborn
- Contact Person Email
- bstein@ump.edu.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
- Department Name
- Dziecięcy Szpital Kliniczny im. J. Polikarpa Brudzińskiego Oddział Kliniczny Neurologii i Pediatrii
- Principal Investigator Name
- Małgorzata Bilska
- Principal Investigator Email
- malgorzata.bilska@uckwum.pl
- Contact Person Name
- Małgorzata Bilska
- Contact Person Email
- malgorzata.bilska@uckwum.pl
- Site Name
- Instytut Pomnik Centrum Zdrowia Dziecka
- Department Name
- Klinika Neurologii i Epileptologii
- Principal Investigator Name
- Katarzyna Kotulska-Joźwiak
- Principal Investigator Email
- neurologia@ipczd.pl
- Contact Person Name
- Katarzyna Kotulska-Joźwiak
- Contact Person Email
- neurologia@ipczd.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Klinika Neurologii Rozwojowej
- Principal Investigator Name
- Maria Mazurkiewicz-Bełdzińska
- Principal Investigator Email
- mmazur@gumed.edu.pl
- Contact Person Name
- Maria Mazurkiewicz-Bełdzińska
- Contact Person Email
- mmazur@gumed.edu.pl
Belgium
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 16-04-2026
- Processing Time Days
- 819
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Neuropediatrics
- Principal Investigator Name
- Helene Verhelst
- Principal Investigator Email
- helene.verhelst@ugent.be
- Contact Person Name
- Helene Verhelst
- Contact Person Email
- helene.verhelst@ugent.be
Netherlands
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 14-02-2025
- Processing Time Days
- 393
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Department of Neurology, sub-department of Pediatric Neurology
- Principal Investigator Name
- Rinze Frederik Neuteboom
- Principal Investigator Email
- r.neuteboom@erasmusmc.nl
- Contact Person Name
- Rinze Frederik Neuteboom
- Contact Person Email
- r.neuteboom@erasmusmc.nl
Hungary
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 16-04-2026
- Processing Time Days
- 819
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- University Of Debrecen
- Department Name
- Gyermekgyógyászati Klinika
- Principal Investigator Name
- Mónika Bessenyei
- Principal Investigator Email
- besmoni@gmail.com
- Contact Person Name
- Mónika Bessenyei
- Contact Person Email
- besmoni@gmail.com
- Site Name
- Semmelweis University
- Department Name
- Gyermekgyógyászati Klinika, Tűzoltó utcai részleg
- Principal Investigator Name
- Márk Kristóf Farkas
- Principal Investigator Email
- kristofm.farkas@gmail.com
- Contact Person Name
- Márk Kristóf Farkas
- Contact Person Email
- kristofm.farkas@gmail.com
Greece
- Earliest CTIS Part Ii Submission Date
- 18-01-2024
- Latest Decision Or Authorization Date
- 17-04-2026
- Processing Time Days
- 820
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- University General Hospital Attikon
- Department Name
- 3rd Pediatric Clinic
- Principal Investigator Name
- Argyrios Dinopoulos
- Principal Investigator Email
- argidino@yahoo.com
- Contact Person Name
- Argyrios Dinopoulos
- Contact Person Email
- argidino@yahoo.com
- Site Name
- St. Luke's Hospital S.A.
- Department Name
- Paediatric Department
- Principal Investigator Name
- Athanasios Evaggeliou
- Principal Investigator Email
- aeevange@auth.gr
- Contact Person Name
- Athanasios Evaggeliou
- Contact Person Email
- aeevange@auth.gr
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- PPD Global Limited
- Responsibilities
- Global CRO
Third parties
- {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"COA management","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Eviden AG","duties_or_roles":"Storage and supply of study equipment","organisation_type":"Industry"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Clinical Outcomes Solutions Limited","duties_or_roles":"Patients and caregivers interviews","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Axon Communications Inc.","duties_or_roles":"Patient Recruitment","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Denmark","full_name":"Unilabs A/S","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient reimbursement, travel arrangements","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"IMP courier service","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Ocrevus 300 mg concentrate for solution for infusion
- Active Substance
- OCRELIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- IV INFUSION
- Route
- IV infusion
- Authorisation Status
- Authorised
- Frequency
- Every 24 weeks (IV infusion)
- Maximum Dose
- maxDailyDoseAmount 600 mg (product record); maxTotalDoseAmount 7200 mg (product record)
- Investigational Product Name
- Gilenya 0.25 mg hard capsules / Gilenya 0.5 mg hard capsules
- Active Substance
- FINGOLIMOD
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Authorised
- Dose Levels
- Formulations referenced: 0.25 mg and 0.5 mg hard capsules
- Frequency
- Once daily (QD) as per prescribing information
- Maximum Dose
- maxDailyDoseAmount 0.5 mg (product record)
- Investigational Product Name
- Placebo for FINGOLIMOD
- Modality
- Other
- Authorisation Status
- Not applicable
- Investigational Product Name
- Placebo for Ocrelizumab
- Modality
- Other
- Authorisation Status
- Not applicable
- Investigational Product Name
- Methylprednisolon acis 250 mg / 1000 mg (auxiliary)
- Active Substance
- METHYLPREDNISOLONE SODIUM SUCCINATE
- Modality
- Small molecule
- Routes Of Administration
- IV INFUSION
- Route
- IV infusion
- Authorisation Status
- Authorised
- Maximum Dose
- maxDailyDoseAmount 100 mg (product record)
- Investigational Product Name
- Reisetabletten AL Dimenhydrinat 50 mg (auxiliary)
- Active Substance
- DIMENHYDRINATE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Authorised
- Maximum Dose
- maxDailyDoseAmount 1 DF dosage form (product record)
Related trials
Other published trials that may interest you.