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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
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
University of Colorado Denver Childrens Hospital Rocky Mountain MS Center
Aurora, Colorado, United States
Childrens National Health Center
Washington D.C., District of Columbia, United States
Boston Childrens Hospital
Boston, Massachusetts, United States
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).
Time frame: 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).
Time frame: 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
Time frame: At Week 24
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.
Time frame: Up to 7 years
Dose Exploration Period: Level of Circulating T Cells and Natural Killer (NK) Cells
Time frame: At Week 24
OOE Period: Level of Circulating T Cells and NK Cells
Time frame: Up to 5 years
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Washington Universtiy school of Medicine
St Louis, Missouri, United States
Cleveland Clinic
Cleveland, Ohio, United States
Ospedale Pediatrico Bambino Gesù
Rome, Lazio, Italy
Azienda Ospedaliera Sant'Andrea
Rome, Lazio, Italy
AOU Policlinico V. Emanuele - P.O G. Rodolico
Catania, Sicily, Italy
Uniwersyteckie Centrum Kliniczne
Gda?sk, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, Poland
...and 2 more locations
Dose Exploration Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte
Time frame: At Week 24
OOE Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte
Time frame: Up to 5 years
Developmental Milestones - Growth Velocity: Change in Height
Time frame: Up to 7 years
Developmental Milestones: Bone Age Assessment by Wrist/Hand Radiographs
Time frame: Up to 7 years
Developmental Milestones: Male and Female Puberty Assessed by Tanner Staging
Time frame: Up to 7 years
Developmental Milestones: Age at Menarche, Related With the Female Reproductive Status
Time frame: 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.
Time frame: Up to Week 24
OOE Period: Number of Participants With Shift From Baseline in Non-MS CNS Pathology as Measured by Brain MRI
Time frame: Up to 5 years
Dose Exploration Period: Levels of Blood Immunoglobulins
Time frame: At Week 24
OOE Period: Levels of Blood Immunoglobulins
Time frame: 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.
Time frame: At Week 24
OOE Period: Number of Participants With Antibody Titers Against Standard Vaccines
Time frame: Up to 5 years
Dose Exploration Period: Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
Time frame: At Week 24
OOE Period: Number of Participants With ADAs to Ocrelizumab
Time frame: Up to 5 years