A Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis

An Open-Label, Parallel-Group Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis

This 2-year study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic (PD) effects of ocrelizumab in children and adolescents ages ≥ 10 to ≤ 18 years with relapsing-remitting multiple sclerosis (RRMS). The data from this study will serve to determine the dosing regimen of ocrelizumab to be further investigated in the subsequent Phase III study in children and adolescents.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Ocrelizumab

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Lazio
    • Rome, Lazio, Italy, 00165
      • Ospedale Pediatrico Bambino Gesu
    • Rome, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
  • Sicily
    • Catania, Sicily, Italy, 95123
      • AOU Policlinico V. Emanuele - P.O G. Rodolico
• 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
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Childrens National Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington Universtiy school of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body weight >/= 25 kg
• Children and adolescents must have received all childhood required vaccinations
• Female participants of childbearing potential must agree to either remain completely abstinent or to use reliable means of contraception
• Diagnosis of relapsing-remitting multiple sclerosis (RRMS)
• Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
• Neurologic stability for >/= 30 days prior to screening, and between screening and baseline
• Participants naive to prior disease-modifying therapy (DMT)
• Participants who have had at least 6 contiguous months of DMT within the past 1 year must have evidence of disease activity occurring after the full 6-month course of treatment, that is, at least one relapse or >/= 1 Gd-enhancing lesion(s) on a T1-weighted brain MRI

Exclusion Criteria:

• Known presence or suspicion of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis, neuromyelitis optica or neuromyelitis optica spectrum disorders and any neurologic, somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development
• Patients that are aquaporin 4 positive and myelin oligodendrocyte glycoprotein (MOG) antibody positive are not eligible to participate in the study.
• In case of an ADEM-like appearance of the first MS attack, a second attack with clear MS-like features is required.
• Infection requiring hospitalization or treatment with IV anti-infective agents
• History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)
• Receipt of a live or live-attenuated vaccine within 6 weeks prior to treatment allocation
• History or laboratory evidence of coagulation disorders
• Peripheral venous access that precludes IV administration and venous blood sampling
• Inability to complete a magnetic resonance imaging (MRI) scan
• History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ
• History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibody (mAbs) or known hypersensitivity to any component of ocrelizumab solution
• Previous treatment with B-cell-targeted therapies
• Percentage of CD4 < 30%
• Absolute Neutrophil Count < 1.5x1000/microliter
• Lymphocyte count below the lower limit of normal (LLN) for age- and sex-specific reference range

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants with a body weight from >/= 25 kg to < 40 kg (with at least 2 participants with a body weight from >/= 25 kg to </= 35 kg) will receive 300 milligram (mg) ocrelizumab	Drug: Ocrelizumab; Ocrelizumab is administered as two infusions of half the dose given 14 days apart for the first dose, then subsequent doses are administered as a single infusion every 24 weeks. Cohort 1: total dose of 300 mg Cohort 2: total dose of 600 mg Cohort 3 and 4: additional dose level(s) may be lower than 300 mg, between 300 mg and 600 mg, or higher than 600 mg, but will be no higher than 1200 mg
Experimental: Cohort 2; Participants with a body weight >/= 40 kg (with at least 2 participants with a body weight >/= 40 kg but </= 50 kg) will receive 600 mg ocrelizumab	Drug: Ocrelizumab; Ocrelizumab is administered as two infusions of half the dose given 14 days apart for the first dose, then subsequent doses are administered as a single infusion every 24 weeks. Cohort 1: total dose of 300 mg Cohort 2: total dose of 600 mg Cohort 3 and 4: additional dose level(s) may be lower than 300 mg, between 300 mg and 600 mg, or higher than 600 mg, but will be no higher than 1200 mg
Experimental: Cohort 3 (optional); Based on PK, PD, safety, and tolerability data analyses of Cohorts 1 and 2, additional participants with a body weight from >/= 25 kg to < 40 kg may be enrolled and receive another dose level of ocrelizumab	Drug: Ocrelizumab; Ocrelizumab is administered as two infusions of half the dose given 14 days apart for the first dose, then subsequent doses are administered as a single infusion every 24 weeks. Cohort 1: total dose of 300 mg Cohort 2: total dose of 600 mg Cohort 3 and 4: additional dose level(s) may be lower than 300 mg, between 300 mg and 600 mg, or higher than 600 mg, but will be no higher than 1200 mg
Experimental: Cohort 4 (optional); Based on PK, PD, safety, and tolerability data analyses of Cohorts 1 and 2, additional participants with a body weight >/= 40 kg may be enrolled and receive another dose level of ocrelizumab	Drug: Ocrelizumab; Ocrelizumab is administered as two infusions of half the dose given 14 days apart for the first dose, then subsequent doses are administered as a single infusion every 24 weeks. Cohort 1: total dose of 300 mg Cohort 2: total dose of 600 mg Cohort 3 and 4: additional dose level(s) may be lower than 300 mg, between 300 mg and 600 mg, or higher than 600 mg, but will be no higher than 1200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Exploration Period: Area Under the Concentration Versus Time Curve of Ocrelizumab	The population PK model was used to simulate concentration-time course and predict individual area under the concentration versus time curve. The data for the PK parameter: area under the concentration versus time curve was collected and analyzed as per body weight range (<40kg to ≥40 kg).	Pre-dose 5- 30 minutes and post-dose 30 mins on Days 1, 15 and 169; At any time on Days 29, 57, 85 and 113
Dose Exploration Period: Maximum Concentration (Cmax) of Ocrelizumab	The population PK model was used to simulate concentration-time course and predict individual Cmax. The data for the PK parameter: Cmax was collected and analyzed as per body weight range (<40kg to ≥40 kg).	Pre-dose 5- 30 minutes and post-dose 30 mins on Days 1, 15 and 169; At any time on Days 29, 57, 85 and 113
Dose Exploration Period: Levels of CD 19+ B-cell Count in Blood		At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.	Up to 7 years
Dose Exploration Period: Level of Circulating T Cells and Natural Killer (NK) Cells		At Week 24
OOE Period: Level of Circulating T Cells and NK Cells		Up to 5 years
Dose Exploration Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte		At Week 24
OOE Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte		Up to 5 years
Developmental Milestones - Growth Velocity: Change in Height		Up to 7 years
Developmental Milestones: Bone Age Assessment by Wrist/Hand Radiographs		Up to 7 years
Developmental Milestones: Male and Female Puberty Assessed by Tanner Staging		Up to 7 years
Developmental Milestones: Age at Menarche, Related With the Female Reproductive Status		Up to 7 years
Dose Exploration Period: Number of Participants With Shift From Baseline in Non-MS Central Nervous System (CNS) Pathology as Measured by Brain Magnetic Resonance Imaging (MRI)	The change in the non-MS CNS pathology was assessed using MRI scans.	Up to Week 24
OOE Period: Number of Participants With Shift From Baseline in Non-MS CNS Pathology as Measured by Brain MRI		Up to 5 years
Dose Exploration Period: Levels of Blood Immunoglobulins		At Week 24
OOE Period: Levels of Blood Immunoglobulins		Up to 5 years
Dose Exploration Period: Number of Participants With Antibody Titers Against Standard Vaccines	Measurement of antibody titers to common antigens (mumps, rubella, varicella, and Streptococcus pneumoniae [S. pneumoniae]) were performed.	At Week 24
OOE Period: Number of Participants With Antibody Titers Against Standard Vaccines		Up to 5 years
Dose Exploration Period: Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab		At Week 24
OOE Period: Number of Participants With ADAs to Ocrelizumab		Up to 5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Actual): October 5, 2023
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Immunologic Factors; Physiological Effects of Drugs; ocrelizumab
• Other Study ID Numbers: WA39085; 2016-002667-34 (EudraCT 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