Once a Month High-dose Methylprednisolone During Wash-out Period Between Natalizumab and Fingolimod Treatments in Patients With Multiple Sclerosis: a Randomised, Controlled, Double-blind Trial (NTZ2FTY)
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- efficacy of high dose methylprednisolone compared to that of a placebo
研究概览
简要总结
Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NTZ) is used in the treatment of relapsing multiple sclerosis (MS). The risk of PML increases after 18 months of treatment. When switching from NTZ to another disease modifying treatment (DMT) in these MS patients with an active disease, there is a high risk of inflammatory reactivation. Nonetheless, a washout period of several weeks is necessary before initiating a new DMT.
The primary purpose of this protocol is to investigate the impact of high dose of oral methylprednisolone, given once a month during the washout period between NTZ and Fingolimod (FTY).
详细描述
Patients with MS receiving NTZ for at least 18 months and without any disease activity during the previous year will be eligible. Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo.
Every patient will initiate a treatment with FTY 7 weeks after the last NTZ perfusion. Methylprednisolone or placebo will be taken 4, 8 and 12 weeks (W4, W8 and W12) after NTZ discontinuation.
A spinal and brain MRI will be performed at baseline (last NTZ perfusion, noted W0) and 16 to 18 weeks after. The last clinical follow-up will be made after 24 weeks.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsing-Remitting Multiple Sclerosis (Mc Donald's 2010 criteria)
- •EDSS<6.0
- •At least18 natalizumab infusions
- •Planned switch from natalizumab to fingolimod
- •Aged between 18 and 65
- •Patients must have received high dose IV methylprednisolone during the 5 previous years
排除标准
- •Progressive MS
- •Uncontrolled MS with natalizumab (existence of a relapse during the previous 12 months or existence of a gadolinium enhancing lesion on a MRI performed during the last 12 months)
- •SEP de forme progressive
- •Contra-indication to the use of high dose oral methylprednisolone
- •Marked cognitive impairment altering protocole understanding
- •Switch from natalizumab to a disease modifying treatment different from fingolimod
- •Contra-indication to fingolimod use
- •Existence of a disease or condition that could alter study completion
- •Chronic treatment with steroids
- •Acute treatment with steroids (more than 300mg during the month prior to inclusion)
- •Contra-indication to gadolinium containing products injection
- •Pregnancy
研究组 & 干预措施
Methylprednisolone
The primary purpose of this protocol is to investigate the impact of high dose of oral methylprednisolone, given once a month during the washout period between NTZ and Fingolimod (FTY).
干预措施: Methylprednisolone (Drug)
Methylprednisolone
The primary purpose of this protocol is to investigate the impact of high dose of oral methylprednisolone, given once a month during the washout period between NTZ and Fingolimod (FTY).
干预措施: natalizumab (NTZ) (Drug)
Methylprednisolone
The primary purpose of this protocol is to investigate the impact of high dose of oral methylprednisolone, given once a month during the washout period between NTZ and Fingolimod (FTY).
干预措施: fingolimob (FTY) (Drug)
Placebo
Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo
干预措施: Placebo (Drug)
结局指标
主要结局
efficacy of high dose methylprednisolone compared to that of a placebo
时间窗: at 6 months
To evaluate the efficacy of high dose methylprednisolone given once a month during the washout period for the switch between natalizumab and fingolimod, compared to that of a placebo, on multiple sclerosis inflammatory rebound evaluated using MRI, 16 to 18 weeks after natalizumab discontinuation and clinically at 6 months
次要结局
- use of methylprednisolone once every 4 weeks during the switch between natalizumab and fingolimod in patients with MS(at 6 months)
- comparison of the number of new T2 or gadolinium enhanced lesions on MRI in the 2 treatment groups(at 4 months)
- adverse effects of high dose oral prednisolone(at 6 months)
- comparison of the number of MS relapses during the 6 months after natalizumab discontinuation, in the 2 treatment groups(at 6 months)
- potential correlations between previous MS activity and the risk of relapse or inflammatory rebound on MRI after natalizumab discontinuation(at 6 months)