A Study of Ocrelizumab in Children and Adolescents With Relapsing-Remitting Multiple Sclerosis
- Registration Number
- NCT04075266
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 23
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Ocrelizumab 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 Cohort 4 (optional) Ocrelizumab 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 Cohort 2 Ocrelizumab 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 Cohort 3 (optional) Ocrelizumab 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
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method OOE Period: Level of Circulating T Cells and NK Cells Up to 5 years Number of Participants With Adverse Events (AEs) Up to 7 years 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.
Dose Exploration Period: Level of Circulating T Cells and Natural Killer (NK) Cells At Week 24 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) Up to Week 24 The change in the non-MS CNS pathology was assessed using MRI scans.
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 At Week 24 Measurement of antibody titers to common antigens (mumps, rubella, varicella, and Streptococcus pneumoniae \[S. pneumoniae\]) were performed.
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
Trial Locations
- Locations (12)
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliera Sant'Andrea
🇮🇹Roma, Lazio, Italy
AOU Policlinico V. Emanuele - P.O G. Rodolico
🇮🇹Catania, Sicilia, Italy
Uniwersyteckie Centrum Kliniczne
🇵🇱Gda?sk, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Pozna?, Poland
Dzieci?cy Szpital Kliniczny im. Józefa Polikarpa Brudzi?skiego
🇵🇱Warszawa, Poland
Instytut Pomnik Centrum Zdrowia Dziecka
🇵🇱Warszawa, Poland
University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
🇺🇸Aurora, Colorado, United States
Childrens National Health Center
🇺🇸Washington, District of Columbia, United States
Boston Childrens Hospital
🇺🇸Boston, Massachusetts, United States
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