A 2 Year, Double-blind, Randomized, Multicenter, Active-controlled Core Phase to Evaluate Safety & Efficacy of Daily Fingolimod vs Weekly Interferon β-1a im in Pediatric Patients With Multiple Sclerosis and 5 Year Fingolimod Extension Phase
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 240
- 试验地点
- 87
- 主要终点
- Frequency of Relapses in Patients Treated for up to 24 Months
研究概览
简要总结
To evaluate the safety and efficacy of fingolimod vs. interferon beta-1a i.m. in pediatric patients with multiple sclerosis (MS)
详细描述
The study is divided into a Core Phase, which includes the Double-Blind Treatment Period, and an Extension Phase in which all patients will be treated with fingolimod. The Core Phase is a 24-month, double-blind, randomized, active-controlled, parallel-group multicenter study phase to evaluate the efficacy and safety of fingolimod compared to IFN β-1a in children/adolescent patients aged 10-17 years old with MS. The Extension Phase is a 60-month (5 year) study phase for patients who complete the Core Phase of the study and meet all inclusion/exclusion criteria and for patients who will be recruited in the younger cohort to participate in the Extension Phase. The 'younger cohort' refers to the population of pediatric patients fulfilling any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage <2). The recruitment of the younger cohort (up to 25 patients) was requested as a post- approval health authority commitment
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
- Double (Participant, Investigator)
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
- •Core Phase:
- •diagnosis of multiple sclerosis
- •at least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of Gd enhancing lesions on MRI within 6 months EDSS score of 0 to 5.5, inclusive
排除标准
- •Core Phase:
- •patients with progressive MS
- •patients with an active, chronic disease of the immune system other than MS
- •patients meeting the definition of ADEM
- •patients with severe cardiac disease or significant findings on the screening ECG.
- •patients with severe renal insufficiency
- •Key Inclusion Criteria Extension Phase:
- •Applies to all patients participating in the Core Phase and then entering the Extension Phase.
- •Patients that originally met Core Phase Inclusion criteria and completed the Core phase on or off of study drug.
- •Applies to patients newly recruited to participate in the Extension Phase.
- •All newly recruited patients' that enroll directly into the Extension Phase must fulfill the local country health authority product label approved for pediatric age group for inclusion criteria.
- •Central review (including initial MRI report) of the diagnosis of pediatric MS will be required for all newly recruited patients.
- •Key Exclusion Criteria Extension Phase:
- •Applies to patients who completed the Core Phase, but prematurely discontinued study drug.
- •Premature discontinuation of the study drug during the Core Phase due to:
- •an adverse event,
- •serious adverse event,
- •laboratory abnormality
- •other conditions leading to permanent study drug discontinuation due to safety reasons
- •Patients with known new events or concomitant medications (washout periods required prior to Visit 15) that would exclude them from the Core Phase exclusion criteria. Serological or other additional tests will not be required.
- •Applies to patients newly recruited in the younger cohort to participate in the Extension Phase.
- •1. All newly recruited patients in the younger cohort that enroll directly into the Extension Phase must fulfill the exclusion criteria for the core phase.
研究组 & 干预措施
Fingolimod
Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose. Participants in this arm during core continued into extension and received open-label treatment
干预措施: Fingolimod (Drug)
Fingolimod
Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose. Participants in this arm during core continued into extension and received open-label treatment
干预措施: Placebo capsule (Drug)
Interferon beta-1a
An intramuscular (IM) injection of Interferon beta-1a was administered once weekly during core phase. Participants switched to receive open-label fingolimod in extension phase
干预措施: Placebo i.m. injection (Drug)
Interferon beta-1a
An intramuscular (IM) injection of Interferon beta-1a was administered once weekly during core phase. Participants switched to receive open-label fingolimod in extension phase
干预措施: Interferon beta-1a (Drug)
Fingolimod-Younger Cohort
The 'younger cohort' refers to the new pediatric patients to be recruited in the extension phase who fulfill any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage <2)
干预措施: Fingolimod (Drug)
结局指标
主要结局
Frequency of Relapses in Patients Treated for up to 24 Months
时间窗: 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
- Time to First Relapse(24 months)
- T1 Gd- Enhancing Lesions(24 months)
- Proportion of Patients Relapse-free(24 months)
- Pharmacokinetics (Cavg) of Fingolimod-P(24 months)
- New/Newly Enlarged T2 Lesions(24 months)
- Pharmacokinetic/Pharmacodynamic Relationship for Fingolimod-P to Lymphocyte Levels(24 months)