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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 23
- 试验地点
- 24
- 主要终点
- Dose Exploration Period: Area Under the Concentration Versus Time Curve of Ocrelizumab
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Ocrelizumab (Drug)
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
干预措施: Ocrelizumab (Drug)
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
干预措施: Ocrelizumab (Drug)
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
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Dose Exploration Period: Area Under the Concentration Versus Time Curve of Ocrelizumab
时间窗: 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
时间窗: 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
时间窗: At Week 24
次要结局
- 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)
- 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)
- 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)
- 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)
- Number of Participants With Adverse Events (AEs)(Up to 12 years)
- OOE Period: Level of Circulating T Cells and NK Cells(Up to 12 years)
- OOE Period: Level of Circulating Lymphocyte, Neutrophil, Monocyte and Leukocyte(Up to 12 years)
- Developmental Milestones: Bone Age Assessment by Wrist/Hand Radiographs(Up to 12 years)
- Developmental Milestones - Growth Velocity: Change in Height(Up to 12 years)
- Developmental Milestones: Male and Female Puberty Assessed by Tanner Staging(Up to 12 years)
- Developmental Milestones: Age at Menarche, Related With the Female Reproductive Status(Up to 12 years)
- OOE Period: Number of Participants With Shift From Baseline in Non-MS CNS Pathology as Measured by Brain MRI(Up to 12 years)
- OOE Period: Levels of Blood Immunoglobulins(Up to 12 years)
- OOE Period: Number of Participants With Antibody Titers Against Standard Vaccines(Up to 12 years)
- OOE Period: Number of Participants With ADAs to Ocrelizumab(Up to 12 years)