A 2-year Randomized, 3-arm, Double-blind, Non-inferiority Study Comparing the Efficacy and Safety of Ofatumumab and Siponimod Versus Fingolimod in Pediatric Patients With Multiple Sclerosis Followed by an Open-label Extension
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 129
- 试验地点
- 56
- 主要终点
- Annualized relapse rate (ARR) in target pediatric participants
研究概览
简要总结
Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis
详细描述
The study is divided into a Core Part and Extension Part. The Core Part is a 24-month, double-blind, triple dummy, randomized, 3-arm active-controlled in children/adolescent patients aged 10-17 years old with Multiple Sclerosis (MS). The Extension Part is 60-month (5 year) open label (except for first 12 weeks transition which will remain double-blind) treatment for patients who complete the Core Part of the study and meet all inclusion/exclusion criteria. The targeted enrollment is 120 participants with multiple sclerosis which will include at least 5 participants with body weight (BW) ≤40 kg and at least 5 participants with age 10 to 12 years in each of the ofatumumab and siponimod arms. There is a minimum 6 month follow up period for all participants (core and extension). Total duration of the study could be up to 7 years.
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)
盲法说明
The core part of the study and the first 12 weeks of the extension period (transition) will be double-blinded and the remainder of the extension period will be open label.
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
- •Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
- •Diagnosis of multiple sclerosis
- •EDSS score of 0 to 5.5, inclusive
- •At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior or evidence of one or more new T2 lesions within 12 months
排除标准
- •Participants with progressive MS
- •Participants with an active, chronic disease of the immune system other than MS
- •Participants meeting the definition of ADEM
- •Participants with severe cardiac disease or significant findings on the screening ECG.
- •Participants with severe renal insufficiency
研究组 & 干预措施
ofatumumab - 20 mg injection/ placebo
Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight).
干预措施: Ofatumumab placebo (Other)
siponimod - 0.5 mg, 1 mg or 2 mg/ placebo
Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).
干预措施: Siponimod (Drug)
siponimod - 0.5 mg, 1 mg or 2 mg/ placebo
Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).
干预措施: Siponimod placebo (Other)
fingolimod - 0.5 mg or 0.25 mg/ placebo
Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).
干预措施: Fingolimod placebo (Other)
ofatumumab - 20 mg injection/ placebo
Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight).
干预措施: Ofatumumab (Drug)
fingolimod - 0.5 mg or 0.25 mg/ placebo
Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).
干预措施: Fingolimod (Drug)
结局指标
主要结局
Annualized relapse rate (ARR) in target pediatric participants
时间窗: Baseline up to 24 months
Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).
次要结局
- Annualized relapse rate (ARR) as compared to historical interferon β-1a data(Baseline up to 24 months)
- Number of adverse events and serious adverse events(Baseline up approximately 66 months)
- Annualized T2 lesion rate(Baseline up to 24 months)
- Plasma Concentrations of siponimod(Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12)
- Neurofilament light chain (NfL) concentrations(Day 1, Months 3,6,12,18,24)
- Plasma Concentrations of ofatumumab(Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24)
- Plasma Concentrations of siponimod metabolite (M17)(Pre-dose Month 3, 5 and Month 12)
- Percentage of participants with anti-ofatumumab antibodies(Day 1, Pre-Dose Months 2,3,5,6,12,18,24)