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AttackMS - Treatment of People With Inflammatory Demyelination Suggestive of MS, or Definite MS, at First Presentation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05418010
Recruitment Status : Not yet recruiting
First Posted : June 14, 2022
Last Update Posted : June 14, 2022
Sponsor:
Information provided by (Responsible Party):
Queen Mary University of London

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Natalizumab

Arm Intervention/treatment
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
Drug: Placebo
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®.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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 ]
  3. 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 ]
  4. 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.


  5. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participant has provided informed consent.
  2. Age 18-45 years
  3. Participant with CIS or MS at first presentation.
  4. Participants show two or more lesions on T2 weighted MRI suggestive of demyelination.
  5. Participant is willing and able to comply with clinical visits and procedures outlined in the study protocol.

Exclusion Criteria:

  1. Hypersensitivity to Tysabri® or to any of the following excipients;

    • Sodium phosphate, monobasic, monohydrate
    • Sodium phosphate, dibasic, heptahydrate
    • Sodium chloride
    • Polysorbate 80 (E433)
    • Water for injections
  2. Evidence of two or more chronic demyelinating hypo-intensities brain lesions 'black holes' on gadolinium-enhanced screening MRI.
  3. Participants with increased risk for opportunistic infections, including immunocompromised participants (those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies).
  4. Combination with other Disease Modifying Treatments..
  5. Known active malignancies, except for participants with cutaneous basal cell carcinoma.
  6. Implants such as pacemaker, aneurysm clip in the brain and MRI-incompatible prosthetic heart valves.
  7. Significant comorbidities such as cardiac failure, renal failure, uncontrolled diabetes and uncontrolled hypercholesterolemia.
  8. History of stroke, thrombosis and/or myocardial infarction.
  9. Any other infection deemed, in the assessment of the PI or sub-investigator, clinically significant.
  10. Claustrophobia
  11. Pregnancy or breastfeeding

Information from the National Library of Medicine

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


Contacts
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Contact: Klaus Schmierer +44 20 7882 6246 k.schmierer@qmul.ac.uk
Contact: Victoria Hammond attackms@qmul.ac.uk

Sponsors and Collaborators
Queen Mary University of London
Investigators
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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
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Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT05418010    
Other Study ID Numbers: 1003822
2021-002255-11 ( EudraCT Number )
First Posted: June 14, 2022    Key Record Dates
Last Update Posted: June 14, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Queen Mary University of London:
Multiple Sclerosis
Magnetic Resonance Imaging (MRI)
Neurofilament light chain
Demyelinating Diseases
Immunologic Factors
Immune System Diseases
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Tysabri
Additional relevant MeSH terms:
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Multiple Sclerosis
Demyelinating Diseases
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Autoimmune Diseases
Immune System Diseases
Natalizumab
Immunologic Factors
Physiological Effects of Drugs