AttackMS: Natalizumab for the Treatment of People With Inflammatory Demyelination Suggestive of Multiple Sclerosis, or Definite Multiple Sclerosis, at First Presentation

简要总结

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). Natalizumab (Tyruko®) is a medication currently approved by the Medicines and Healthcare products Regulatory Agency (MHRA) as a disease-modifying treatment for adults with rapidly evolving severe (RES) relapsing MS. We are looking to test safety and efficacy of treatment with Tyruko® 300mg, given through a needle in a vein (intravenous infusion), over 20 weeks and to advance mechanistic understanding in treating people with first presentation of CIS or MS. AttackMS will test the effect of starting a highly-effective DMT licensed for MS, Tyruko®, within a short time - 14 days - after symptom onset. The main objective is to test Tyruko®, given intravenously every 4 weeks over 20 weeks, for safety, efficacy, and to advance the mechanistic understanding of the earliest events in inflammatory demyelination/MS.

主要结局

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)