A Phase III Multicenter, Randomized, Double-blind, Double-dummy Study to Evaluate Safety and Efficacy of Ocrelizumab in Comparison With Fingolimod in Children and Adolescents With Relapsing-remitting Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 188
- 试验地点
- 173
- 主要终点
- Annualized Relapse Rate (ARR)
研究概览
简要总结
This double-blind, double-dummy study will evaluate the safety and efficacy of ocrelizumab compared with fingolimod in children and adolescents with RRMS aged between 10 and < 18 years over a flexible duration. The double-blind period will last until after the last participant randomized has completed 24 weeks.
详细描述
This Phase III randomized, double-blind, double-dummy, multicenter study will evaluate the safety and efficacy of ocrelizumab administered as intravenous (IV) infusion every 24 weeks (Q24W) compared with fingolimod taken orally (PO), once daily (QD), in children and adolescents with RRMS aged between 10 and < 18 years. Participants will be randomized in a 1:1 ratio (ocrelizumab:fingolimod), globally. This study consists of a double-blind, double dummy period in which participants will be treated with either active ocrelizumab or active fingolimod for a flexible duration. Participants who complete the double-blind period will be offered the possibility to enter an optional open-label extension (OLE) treatment period of at least 144 weeks with ocrelizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Body weight ≥ 25 kg
- •Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric multiple sclerosis (MS), Version 2012, or McDonald criteria 2017
- •Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
- •For all countries except Germany, at least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of at least one Gd-enhancing lesion on MRI within 6 months prior to randomization
- •Inclusion Criteria for Optional OLE Period:
- •Participants in Group A (ocrelizumab in the DBP) and Group B (fingolimod in the DBP) who, in the opinion of the investigator, may benefit from switching to ocrelizumab and who have completed the DBP with study treatment (ocrelizumab/fingolimod), may participate in the OLE period
排除标准
- •Known presence or suspicion of other neurologic disorders that may mimic MS
- •Significant uncontrolled somatic diseases, known active infection or any other significant condition that may preclude participant from participating in the study
- •Participants with severe cardiac disease or significant findings on the screening electrocardiograph (ECG)
- •Exclusion Criteria for Optional OLE Period:
- •Participants who have discontinued the study during the DBP
研究组 & 干预措施
Ocrelizumab
Participants will receive ocrelizumab, as IV infusion Q24W. The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15, and subsequent doses are given as single infusions of ocrelizumab Q24W. Participants will also receive a placebo of fingolimod administered as QD capsule.
干预措施: Ocrelizumab (Drug)
Ocrelizumab
Participants will receive ocrelizumab, as IV infusion Q24W. The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15, and subsequent doses are given as single infusions of ocrelizumab Q24W. Participants will also receive a placebo of fingolimod administered as QD capsule.
干预措施: Fingolimod Placebo (Other)
Fingolimod
Participants will receive fingolimod PO, QD as per the prescribing information provided with fingolimod. Participants will also receive a placebo of ocrelizumab administered as IV infusion on Days 1 and 15, and Q24W thereafter.
干预措施: Ocrelizumab Placebo (Other)
Fingolimod
Participants will receive fingolimod PO, QD as per the prescribing information provided with fingolimod. Participants will also receive a placebo of ocrelizumab administered as IV infusion on Days 1 and 15, and Q24W thereafter.
干预措施: Fingolimod (Drug)
结局指标
主要结局
Annualized Relapse Rate (ARR)
时间窗: Baseline up to approximately 4 years
Protocol-defined Annualized Relapse Rate (ARR)
时间窗: Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks)
The population-level summary is rate ratio of ARR. The ARR is calculated as the total number of protocol-defined relapses divided by the total patient-years. Protocol-defined relapse is the occurrence of new/worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by relatively stable or improving neurological state for ≥ 30 days. Symptoms must persist for \>24 hours \& should not be attributable to confounding clinical factors. The new/worsening neurological symptoms must be accompanied by objective neurological worsening consistent with an increase of at least half a step on the expanded disability status scale (EDSS) score, or 2 points on one of the appropriate functional system (FS) scores, or 1 point on two or more of the appropriate FS scores. The change must affect the selected FS (i.e., pyramidal, ambulation, cerebellar, brainstem, sensory, or visual). Adjusted values were reported. OM assessed non inferiority of ocrelizumab vs fingolimod.
次要结局
- Number of New or Enlarging T2-hyperintense Lesions (T2 lesions) as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-blind Period(Baseline up to approximately 4 years)
- Number of New or Enlarging T2 Lesions by Week 96(Baseline up to Week 96)
- ARR by Week 96(Baseline up to Week 96)
- Number of T1 Gadolinium (Gd) Lesions at Week 12(Week 12)
- Incidence and Severity of Adverse Events (AEs), With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)(Baseline up to approximately 8 years)
- Prevalence of Anti-drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study(Baseline up to approximately 8 years)
- Protocol-defined ARR(Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks))
- Number of New or Enlarging T2-hyperintense Lesions (T2 Lesions), as Detected by Brain Magnetic Resonance Imaging (MRI)(Up to after the last participant randomized completed 24 weeks since first study treatment administration (up to approximately 160 weeks))
- Number of T1 Gd Lesions at Week 12(At Week 12)
- Number of Participants With Adverse Events (AEs)(Up to approximately 7 years)
- Maximum Serum Concentration (Cmax) of Ocrelizumab(Cycle (1 Cycle=24 weeks))
- Area Under the Plasma Concentration-time Curve Over a Dosing Interval (AUC Tau) of Ocrelizumab(Cycle 1 (1 Cycle=24 weeks))
- Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab(Up to approximately 7 years)
- Levels of Cluster of Differentiation 19 (CD19) + B-cell Count in Blood(Up to approximately 7 years)