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

NCT04075266 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: WA390852016-002667-34
• Study Type: interventional
• Target: 23
• Locations: 3 countries
• Sites: 12

Brief Summary

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (17)

• Number of Participants With Adverse Events (AEs)

  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

Study Arms (4)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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

Cohort 3 (optional)

EXPERIMENTAL

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

Cohort 4 (optional)

EXPERIMENTAL

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

Interventions

Ocrelizumab DRUG

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

Cohort 1; Cohort 2; Cohort 3 (optional); Cohort 4 (optional)

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (12)

University of Colorado Denver Childrens Hospital Rocky Mountain MS Center

Aurora, Colorado, 80045, United States

Location

Childrens National Health Center

Washington D.C., District of Columbia, 20010, United States

Location

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

Location

Washington Universtiy school of Medicine

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 00165, Italy

Location

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, 00189, Italy

Location

AOU Policlinico V. Emanuele - P.O G. Rodolico

Catania, Sicily, 95123, Italy

Location

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-952, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, 60-355, Poland

Location

Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego

Warsaw, 02-091, Poland

Location

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Related Publications (1)

• 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.

  PMID: 39812825 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 30, 2019
• Study Start: January 9, 2020
• Primary Completion: October 5, 2023
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 23, 2025
• Results First Posted: November 8, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (5); IT (3); PL (4)