AttackMS - Treatment of People With Inflammatory Demyelination Suggestive of MS, or Definite MS, at First Presentation
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|ClinicalTrials.gov Identifier: NCT05418010|
Recruitment Status : Not yet recruiting
First Posted : June 14, 2022
Last Update Posted : June 14, 2022
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 (Tysabri®) 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 Tysabri® 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, Tysabri®, within a short time - 14 days - after symptom onset. The main objective is to test Tysabri®, 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
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis Clinically Isolated Syndrome of Demyelination||Drug: Tysabri Injectable Product Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Natalizumab for the Treatment of People With Inflammatory Demyelination Suggestive of Multiple Sclerosis, or Definite Multiple Sclerosis, at First Presentation|
|Estimated Study Start Date :||July 31, 2022|
|Estimated Primary Completion Date :||August 31, 2023|
|Estimated Study Completion Date :||August 31, 2024|
Active Comparator: Tysabri® 300mg
Tysabri® 300mg, administered via intravenous infusion in a 4 week cycle, for a total of 6 cycles
Drug: Tysabri Injectable Product
Tysabri® is indicated as single disease modifying therapy in adults with highly active relapsing remitting multiple sclerosis. Tysabri® 300mg concentrate for solution for infusion and matching placebo are collectively referred to as IMP when detailing to blinded trial procedures. Tysabri® 300mg will be colourless, clear to slightly opalescent solution.
Other Name: Natalizumab
Placebo Comparator: Placebo
Placebo, administered via intravenous infusion in a 4 week cycle, for 3 cycles, followed by Tysabri® 300mg, administered via intravenous infusion for a total of 3 cycles
Placebo is colourless, clear to slightly opalescent liquid. The formulation of the is the same as that of commercial Tysabri® minus the active ingredient. Placebo is in the same containers/vials as Tysabri®.
- To establish whether there is efficacy superiority of Tysabri® over placebo at 12 weeks in facilitating remyelination of previously demyelinated CNS lesions, as measured by MRI lesion magnetization transfer ratio (MTR). [ Time Frame: 12 weeks ]Mean magnetisation transfer ratio (MTR) change in FLAIR-hyper-intense lesions at 12 weeks compared to baseline
- To establish whether there is a difference between participants receiving Tysabri® or placebo at 24 weeks in P100 latency measured using visually evoked potentials (VEP). [ Time Frame: 0 and 24 weeks ]P100 latency in each eye at week 24 compared to baseline. Inter-ocular P100 latency difference at week 24 compared to baseline.
- To establish whether there is a difference between participants receiving Tysabri® or placebo at 24 weeks in number and occurrence of adverse events. [ Time Frame: 24 weeks ]
- To establish whether there is a difference between participants receiving Tysabri® or placebo at 24 weeks in facilitating remyelination of previously demyelinated CNS lesions using Magnetisation transfer ratio (MTR). [ Time Frame: 0, 12 and/or 24 weeks ]
- To establish whether there is a difference between participants receiving Tysabri® or placebo at 24 weeks in protecting limb function. [ Time Frame: 24 weeks ]
Serum-neurofilament light chain levels (SNfL) at week 24 compared to baseline. Expanded Disability Status Scale (EDSS) at week 24 compared to baseline. SDMT (Symbol Digit Modalities Test) score at week 24 compared to baseline. Lower Limb Function: The T25-FW (Timed 25 Foot Walk) will be collected in all pwMS. able to walk the required distance at week 24 compared to baseline.
9-HPT (Nine Hole Peg Test) at week 24 compared to baseline. NFI-MS (Neurological Fatigue Index-MS) score at week 24 compared to baseline 24 weeks.
- To establish whether there is a difference between participants receiving Tysabri® or placebo at 24 weeks in Retinal nerve fibre layer and ganglion cell + inner plexiform (GCIP) layer thickness measured using optical coherence tomography (OCT). [ Time Frame: O and 24 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05418010
|Contact: Klaus Schmierer||+44 20 7882 email@example.com|
|Contact: Victoria Hammondfirstname.lastname@example.org|
|Principal Investigator:||Klaus Schmierer||Queen Mary University of London|
|Principal Investigator:||Waqar Rashid||St George's University Hospital NHS Foundation Trusts|
|Principal Investigator:||Victoria Singh-Curry||Chelsea and Westminster Hospital Foundation Trust|