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

NCT05418010 | Recruiting Phase 2 DMC

• 2 other identifiers: 10038222021-002255-11
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Clinically Isolated Syndrome of Demyelination; Multiple Sclerosis

Keywords

Multiple Sclerosis; Magnetic Resonance Imaging (MRI); Neurofilament light chain; Demyelinating Diseases; Immunologic Factors; Immune System Diseases; Autoimmune Diseases; Autoimmune Diseases of the Nervous System; Tyruko

Outcome Measures

Primary Outcomes (1)

• 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).

  Mean magnetisation transfer ratio (MTR) change in FLAIR-hyper-intense lesions at 12 weeks compared to baseline

  12 weeks

Secondary Outcomes (5)

• 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

Study Arms (2)

Tyruko® 300mg

ACTIVE COMPARATOR

Tyruko® 300mg, administered via intravenous infusion in a 4 week cycle, for a total of 6 cycles

Drug: Tyruko Injectable Product

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

Placebo is colourless, clear to slightly opalescent liquid. The formulation of the is the same as that of commercial Tyruko® minus the active ingredient. Placebo is in the same containers/vials as Tyruko®.

Placebo

Tyruko Injectable Product DRUG

Tyruko® is indicated as single disease modifying therapy in adults with highly active relapsing remitting multiple sclerosis. Tyruko® 300mg concentrate for solution for infusion and matching placebo are collectively referred to as IMP when detailing to blinded trial procedures. Tyruko® 300mg will be colourless, clear to slightly opalescent solution.

Also known as: Natalizumab

Tyruko® 300mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: collaborator
• UCL Queen Square Institute of Neurology: collaborator
• Moorfields Eye Hospital NHS Foundation Trust: collaborator
• Barts & The London NHS Trust: collaborator
• Queen Mary University of London: lead

Study Sites (2)

Royal London Hospital

London, E1 1FR, United Kingdom

NOT YET RECRUITING

St George's Hospital

London, SW17 0QT, United Kingdom

RECRUITING

Related Links

• AttackMS Abstract
• CI Interview: AttackMS assessing the feasibility of multiple sclerosis treatment within 14 days of presentation
• Multiple Sclerosis Academy Webinar on AttackMS

MeSH Terms

Conditions

Multiple Sclerosis; Charcot-Marie-Tooth disease, Type 1F; Demyelinating Diseases; Immune System Diseases; Autoimmune Diseases; Autoimmune Diseases of the Nervous System

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Klaus Schmierer

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

• Liqun Zhang

  St George's University Hospital NHS Foundation Trusts

  PRINCIPAL INVESTIGATOR

• Victoria Singh-Curry

  Chelsea and Westminster Hospital Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Klaus Schmierer

CONTACT

+44 20 7882 6246; k.schmierer@qmul.ac.uk

Julia Elizabeth Phillips

CONTACT

attackms@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled efficacy trial of hyperacute disease modifying treatment using Tyruko® in people with a first manifestation of central nervous system inflammatory demyelination.

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: June 14, 2022
• Study Start: December 1, 2022
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

GB (2)