AttackMS: Natalizumab for the Treatment of People With Inflammatory Demyelination Suggestive of Multiple Sclerosis, or Definite Multiple Sclerosis, at First Presentation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- To establish whether there is efficacy superiority of Natalizumab (Tyruko®) over placebo at 12 weeks in facilitating remyelination of previously demyelinated CNS lesions, as measured by MRI lesion magnetization transfer ratio (MTR).
研究概览
简要总结
Multiple Sclerosis (MS) is a chronic inflammatory & degenerative disease of the central nervous system (CNS) Recent data from the MS Base registry demonstrated an average delay of 152 - 215 days between first presentation and the diagnosis of MS, and more than one year until Disease Modifying Treatment (DMT) begins.
Evidence suggests that shutting down inflammation using highly effective DMTs early after diagnosis leads to better long term clinical outcomes The AttackMS trial will test the effect of starting a highly-effective DMT licensed for MS, Tyruko® (Natalizumab 300mg), within a short time - 14 days - after symptom onset.
详细描述
MS is a disease of the central nervous system affecting over 130,000 people in the UK and more than 2.8 million worldwide. Left untreated, MS leads to chronic disability in the large majority of cases.
CIS is a common first manifestation of MS: There is a more than 80% chance of MS in somebody presenting with CIS provided one or more "lesions" characteristic of inflammatory demyelination can be detected on a magnetic resonance imaging (MRI) of the brain. The presence of at least two such lesions is an inclusion criterion for this study. Inflammatory demyelination is the process by which cells of your body's own immune system attack the insulation sheath (= myelin) of nerve fibres (= axons) in the central nervous system.
Once a diagnosis of MS has been confirmed, many people with this disease will be eligible for what is called "disease-modifying treatment" (DMT) on the NHS. Such treatment targets the immune cells that are involved in the inflammatory attack against the myelin sheaths and nerve fibres. However, while in a small number of cases, a diagnosis of MS can be made instantaneously it regularly takes week, months and, sometimes even longer, to fulfil the formal diagnostic criteria of MS. This diagnostic delay inevitably leads to delays in starting disease-modifying treatment.
Using a trial concept geared towards rapid assessment of eligibility, and a disease-modifying treatment that is both highly effective and generally well tolerated in people with MS, AttackMS will test whether:
(i) It is feasible to recruit participants with a diagnosis of CIS at high risk of MS, or definite MS, at first presentation for treatment within 14 days of symptom onset and (ii) Such early treatment improves myelin repair at 3 months, as measured using a special MRI technology called magnetisation transfer ratio (MTR).
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
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has provided informed consent.
- •Age 18-55 years
- •Participant with CIS or MS at first presentation.
- •Participants show two or more lesions on T2 weighted MRI suggestive of demyelination.
- •Participant is willing and able to comply with clinical visits and procedures outlined in the study protocol.
排除标准
- •Hypersensitivity to Tyruko® or to any of the following excipients:
- •Histidine
- •Histidine monohydrochloride
- •Sodium chloride
- •Polysorbate 80 (E433)
- •Water for injections
- •Evidence of multiple chronic demyelinating lesions on MRI without signs of recent activity.
- •Participants with increased risk for opportunistic infections, including immunocompromised participants (those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies).
- •Combination with other Disease Modifying Treatments..
- •Known active malignancies, except for participants with cutaneous basal cell carcinoma.
- •Implants such as pacemaker, aneurysm clip in the brain and MRI-incompatible prosthetic heart valves.
- •Significant comorbidities such as cardiac failure, renal failure, uncontrolled diabetes and uncontrolled hypercholesterolemia.
- •History of stroke, thrombosis and/or myocardial infarction.
- •Any other infection deemed, in the assessment of the PI or sub-investigator, clinically significant.
- •Claustrophobia
- •Pregnancy or breastfeeding
研究组 & 干预措施
Tyruko® 300mg
Tyruko® 300mg, administered via intravenous infusion in a 4 week cycle, for a total of 6 cycles
干预措施: Tyruko Injectable Product (Drug)
Placebo
Placebo, administered via intravenous infusion in a 4 week cycle, for 3 cycles, followed by Tyruko® 300mg, administered via intravenous infusion for a total of 3 cycles
干预措施: Placebo (Drug)
结局指标
主要结局
To establish whether there is efficacy superiority of Natalizumab (Tyruko®) over placebo at 12 weeks in facilitating remyelination of previously demyelinated CNS lesions, as measured by MRI lesion magnetization transfer ratio (MTR).
时间窗: 12 weeks
Mean magnetisation transfer ratio (MTR) change in FLAIR-hyper-intense lesions at 12 weeks compared to baseline
次要结局
- To establish whether there is a difference between participants receiving Natalizumab (Tyruko®) or placebo at 24 weeks in P100 latency measured using visually evoked potentials (VEP).(0 and 24 weeks)
- To establish whether there is a difference between participants receiving Natalizumab (Tyruko®) or placebo at 24 weeks in number and occurrence of adverse events.(24 weeks)
- To establish whether there is a difference between participants receiving Natalizumab (Tyruko®) or placebo at 24 weeks in facilitating remyelination of previously demyelinated CNS lesions using Magnetisation transfer ratio (MTR).(0, 12 and/or 24 weeks)
- To establish whether there is a difference between participants receiving Natalizumab (Tyruko®) or placebo at 24 weeks in protecting limb function.(24 weeks)
- To establish whether there is a difference between participants receiving Natalizumab (Tyruko®) or placebo at 24 weeks in Retinal nerve fibre layer ganglion cell + inner plexiform (GCIP) layer thickness measured using optical coherence tomography (OCT).(O and 24 weeks)