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
Study summary
This 12-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.
Eligibility
Sex
ALL
Min age
10 Years
Max age
17 Years
Healthy volunteers
No
Inclusion Criteria:
* Age at screening between =/\>10 to \<18 years
* 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
* 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 acute disseminated encephalomyelitis (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
Primary outcome measure(s)
Dose Exploration Period: Area Under the Concentration Versus Time Curve of Ocrelizumab — 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 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).
Dose Exploration Period: Maximum Concentration (Cmax) of Ocrelizumab — 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 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).
Dose Exploration Period: Levels of CD 19+ B-cell Count in Blood — At Week 24
Trial sites (12)
Facility
City
Region
Status
University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
Aurora
Colorado
Childrens National Health Center
Washington D.C.
District of Columbia
Boston Childrens Hospital
Boston
Massachusetts
Washington Universtiy school of Medicine
St Louis
Missouri
Cleveland Clinic
Cleveland
Ohio
Ospedale Pediatrico Bambino Gesù
Rome
Lazio
Azienda Ospedaliera Sant'Andrea
Rome
Lazio
AOU Policlinico V. Emanuele - P.O G. Rodolico
Catania
Sicily
Uniwersyteckie Centrum Kliniczne
Gda?sk
Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna
Poland
Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego
Warsaw
Poland
Instytut Pomnik Centrum Zdrowia Dziecka
Warsaw
Poland
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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