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Advanced Multiple SclerosisPhase 2/3ChariotMSNCT04695080

ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis

A Phase 2/3 study testing Cladribine (MAVENCLAD®) in people with Advanced Multiple Sclerosis and Progressive Multiple Sclerosis, run by Queen Mary University of London at 22 sites in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

MS is a chronic inflammatory and degenerative disease of the central nervous system (CNS) affecting more than 120,000 people in the UK.and 2.5 million people worldwide. Without disease modifying treatment (DMT),the majority of people with MS (pwMS) will develop significant disability within 10 years of onset, and 50%… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cladribine (MAVENCLAD®)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
204 participants
Where
22 sitesUnited Kingdom
Study dates
25 Jun 2021to 31 Dec 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • pwAMS aged 18+ years with an EDSS of 6.5-8.5 (inclusive)
  • History of bowel cancer screening for men, and women and cervical and breast cancer screening for women as per NHS recommended guidelines https://www.nhs.uk/conditions/nhs-screening/.
  • Ability to complete the 9HPT with at least one upper limb within 180 seconds. The average score of both attempts for each hand should be used to assess eligibility.
  • Confirmation of MS diagnosis according to the McDonald Criteria (2017) Thompson et al. 2018).
  • In the judgement of the investigator, evidence of deterioration of upper limb function during the 2 years running up to the screening date.

Who cannot join

  • Participants with known hypersensitivity to Cladribine of any grade (as per CTCAE grading system) should be excluded
  • Any uncontrolled diabetes, arterial hypertension and hypercholesterolaemia as determined by PI or delegated sub-investigator
  • A history of stroke and/or myocardial infarction
  • Moderate to severe renal impairment (creatinine clearance <60 ml/min)
  • Moderate to severe hepatic impairment (Child-Pugh score >6)
  • Significant comorbidity, e.g. cardiac failure, renal failure, malignancy, or other health condition that in the view of the PI or delegated sub-investigator precludes participation. Patients who, following discussion with their cancer treatment team, are deemed to be cured from malignancy, may be eligible to participate as per the clinical judgement of the local PI.
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  • Pregnancy including planning to father a child or breastfeeding
  • Body weight less <40kg
  • Unwillingness to use effective contraception throughout the trial period until at least six months after the last administration of IMP. This is not applicable for post-menopausal women
  • Acute infection (uncontrolled)
  • Infection with Human Immunodeficiency Virus 1 and/or 2
  • Active chronic infection (Syphilis, Tuberculosis, Hepatitis). Patients with active TB will be excluded. However, patients who have a positive IGRA, Elispot or Quantiferon test, but exhibit no symptoms for TB and evidence of a normal Chest X Ray, can be included in the study as per judgement of the local PI and after clarification with the CI.
  • Precancerous condition
  • Total lymphocyte count <1.0*109/L
  • Seronegativity for varicella zoster virus. Potential participants who are IgG negative may undergo vaccination, and can be screened again once full course has been completed.
  • Seronegativity for all of the following: measles, mumps, rubella. Potential participants who are IgG negative for all 3 viruses, may undergo vaccination and can be screened again once full course has been completed.
  • Relapse within six months before screening
  • Inability to complete an MRI (contraindications for MRI, including but not limited to, MRI-non-compatible pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry in the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, severe anxiety or claustrophobia etc.) or contraindication to Gd administration.
  • Treatment with steroids due to MS relapse/progression within three months of screening. pwAMS who fall in this category may undergo a further screening visit once the three months' window has expired and may be included if no steroid treatment has been administered in the intervening period. If for any reason a participant is unable to have a baseline MRI scan (due for safety reasons), this MRI scan may be omitted and a recent 'historical' MRI scan (collected within the 3 months preceding the first IMP dose dispensing at Baseline visit) can be used at the CI's discretion. This will need to be assessed by the CI case by case basis. The review of the historical MRI scan to exclude PML should be clearly documented in the subject's electronic health records prior to the first IMP dose dispensing at Baseline visit.
  • Treatment with any interferon-beta, glatiramer acetate, teriflunomide, leflunomide or dimethyl-fumarate within three months before screening.
  • Treatment with natalizumab, fingolimod, siponimod, ponesimod, ozanimod (or other Sphingosine-1-phosphate receptor modulators) within three months of screening.
  • Treatment with azathioprine, methotrexate, or cyclosporine within six months before screening.
  • pwAMS treated with teriflunomide will need to undergo accelerated elimination of the compound before being considered (Research and Case Medical Research 2019).
  • Treatment with haematopoietic stem cell transplantation (HSCT), mitoxantrone, cyclophosphamide, cladribine, alemtuzumab, or another B cell depleting compound, such as rituximab, ocrelizumab, ublitiuximab, ofatumumab, or biosimilars, unless the participant concerned has a memory B cell level of ≥20% of the CD19+ population in the peripheral blood. Such a level would normally not be expected earlier than a minimum of six months after the last drug administration. Participants who underwent such treatment will therefore have to be tested for their CD19+/CD27+ memory B cell level at screening.
  • Treatment with fampridine: If they are already on treatment for at least one month, participants should continue throughout the trial. However, starting continuous fampridine treatment after signing the consent sheet will lead to exclusion from treatment with IMP/placebo.
  • Concurrent participation or previous participation within the last 6 months in another clinical trial of an IMP or medical device.
  • Unable to swallow tablets

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United Kingdom22 sites

  • Queens University Belfast (Belfast Health and Social Care Trust)

    Belfast, BT12 6BA

  • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham

    Birmingham, B15 2TH

  • Cardiff University Hospital

    Cardiff, CF14 4XW

  • University Hospitals of Coventry and Warwickshire NHS Trust

    Coventry, CV2 2DX

  • Anne Rowling Clinic, University of Edinburgh

    Edinburgh, EH16 4SB

  • Queen Elizabeth University Hospital Glasgow

    Glasgow, G51 4TF

  • University Hospital Hairmyres, NHS Lanarkshire

    Glasgow, G75 8RG

  • Leeds Teaching Hospitals NHS Trust

    Leeds, LS1 3EX

  • Walton Centre NHS Trust

    Liverpool, L9 7LJ

  • Royal London Hospital

    London, E1 1FR

  • Royal Free London NHS Foundation Trust

    London, NW3 2QG

  • Queen's Hospital (Havering and Redbridge University Hospitals NHS Trust)

    London, RM7 0AG

  • Lewisham and Greenwich NHS Trust

    London, SE13 6LH

  • St George's University Hospitals NHS Foundation Trust

    London, SW17 0RE

  • Luton and Dunstable Hospital

    Luton, LU4 0DZ

  • Salford Royal Hospital NHS Trust

    Manchester, M6 8HD

  • Aneurin Bevan University Health Board

    Newport, NP20 2UB

  • Nottingham University Hospital (Nottingham University Hospitals NHS Trust)

    Nottingham, NG7 2UH

  • University Hospitals Plymouth NHS Trust

    Plymouth, PL6 8DH

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, S10 2JF

  • University Hospitals of North Midlands NHS Trust

    Stoke-on-Trent, ST4 6QG

  • Morriston Hospital, Swansea

    Swansea, SA6 6NL

Other trials in United Kingdom

About this study

Official title: ChariotMS - A National (UK) Phase IIb, Multi-centre, Randomised, Double-blind, Placebo Controlled (1:1) Efficacy Trial With Cost-utility Analysis of Cladribine Tablets (3.5mg/kg Over Two Years) in People With Advanced Multiple Sclerosis. Is Cladribine Superior to Placebo in Protecting Upper Limb Function?

MS is a chronic inflammatory and degenerative disease of the central nervous system (CNS) affecting more than 120,000 people in the UK.and 2.5 million people worldwide.

Without disease modifying treatment (DMT),the majority of people with MS (pwMS) will develop significant disability within 10 years of onset, and 50% will require wheelchair assistance within 20 years. convenient, highly effective and CNS penetrant DMT for patients with relapsing multiple sclerosis (pwRMS) administered in short (8-10 days/year over 2 years) treatment courses.

It effectively depletes B cells, particularly Memory B cells, a likely key mechanism of disease control in MS. Cladribine is the investigational product in this study as it not currently used to treat patients with an EDSS of 6.5 - 8.5. This is a multi-centre, randomised double-blind placebo-controlled phase IIb to test cladribine tablets (MAVENCLAD®) (3.5mg/kg over 24 months) for safety, efficacy, and cost effectiveness, and to advance mechanistic understanding of its action in people with advanced MS (pwAMS).

Being tested
Cladribine (MAVENCLAD®), Placebo
Keywords
Multiple Sclerosis, Progressive multiple sclerosis, Advanced multiple sclerosis, Upper limb function, Cladribine, Quality of life, Cognition, Health Economics, Biomarkers, Neurofilament light chain, B cells, Lymphocytes, Magnetic Resonance Imaging (MRI)
Medical subject headings
Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Charcot-Marie-Tooth disease, Type 1F

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cladribine (MAVENCLAD®)Drug

    Cladribine (MAVENCLAD®) 3.5mg/kg, administered as weight-adjusted 10mg tablets in two treatment courses (12 months apart) lasting 8- 10 days each.

    Cladribine (MAVENCLAD®) 10mg available in blister packs of 1 tablet, 4 tablets and 6 tablets.

  • PlaceboDrug

    Placebo administered as weight adjusted tablets in two treatment courses (12 months apart) lasting 8-10 days each.

    Placebo 10mg available in blister packs of 1 tablet, 4 tablets and 6 tablets.

Study groups in NCT04695080
Study groupRoleWhat they receive
Cladribine (MAVENCLAD®)Active comparatorNot described
Receives: Drug: Cladribine (MAVENCLAD®)
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The 9-HPT peg speed (tasks/second) at 24 months

    To establish whether there is efficacy superiority of cladribine tablets over placebo in reducing deterioration of upper limb function in pwAMS.

    To investigate whether cladribine tablets 3.5mg/kg over 24 months is an effective DMT in pwAMS as measured using the 9-hole peg test (9HPT) peg speed at 24 months.

    Measured: 24 months

  2. 9-HPT proportion of patients who do not deteriorate at 24 months

    Measured: 24 months

Secondary outcomes (19)

  1. Change over 24 months of the study in clinical outcome measure: EDSS

    The proportion of the cladribine versus placebo arms with an increase of >=0.5 in EDSS score over 24 months.

    Measured: Screening, Month 6, 12, 18 and 24

  2. Change over 24 months of the study in clinical outcome measure: ARAT

    ARAT (Upper Limb Function Test) upper limb function test score

    Measured: Screening, Month 6, 12, 18 and 24

  3. Change over 24 months of the study in clinical outcome measure: ABILHAND

    ABILHAND score for manual ability

    Measured: Screening, Month 6, 12, 18 and 24

  4. Change over 24 months of the study in clinical outcome measure: T25ftWT

    Lower Limb Function: The T25ftWT (Timed 25 foot walk test) will be collected in all pwAMS able to walk the required distance twice.

    Measured: Screening, Month 6, 12, 18 and 24

  5. Change over 24 months of the study in clinical outcome measure: SLCVA

    SLCVA (Sloan low contrast letter visual acuity) score.

    Measured: Screening, Month 6, 12, 18 and 24

  6. Change over 24 months of the study in clinical outcome measure: MSIS-29v2

    MSIS-29v2 (Multiple Sclerosis Impact Scale) quality of life score

    Measured: Screening, , Month 6, 12, 18 and 24

  7. Change over 24 months of the study in clinical outcome measure: SDMT

    SDMT (The Symbol Digit Modalities Test) score.

    Measured: Screening, Month 6, 12, 18 and 24

  8. Change over 24 months of the study in clinical outcome measure: NFI-MS

    NFI-MS (Neurological Fatigue Index-Multiple Sclerosis) score.

    Measured: Screening, Month 6, 12, 18 and 24

  9. Change over 24 months of the study in clinical outcome measure: EuroQoL EQ-5D-5L

    Cost-utility: Patient's generic health-related quality of life, measured using the EuroQoL EQ-5D-5L and, separately, carer's generic health-related quality of life, measured using the EuroQoL EQ-5D-5L, health and social care and other costs.

    Measured: Screening, Month 6, 12, 18 and 24

  10. Change over 24 months of the study in clinical outcome measure: EuroQoL EQ-5D-5L

    Cost-utility: Carer's generic health-related quality of life, measured using the EuroQoL EQ-5D-5L

    Measured: Screening, Month 6, 12, 18 and 24

  11. Change over 24 months of the study in clinical outcome measure: EuroQoL EQ-5D-5L

    Cost-utility: health and social care and other costs.

    Measured: Screening, Month 6, 12, 18 and 24

  12. Change over 24 months of the study in clinical outcome measure: WPAI-GH

    WPAI-GH (Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI:GH) score

    Measured: Baseline, Month 6, 12, 18 and 24

  13. Safety/occurrence of adverse events

    Safety:

    • Any AEs/SAEs,
    • Lymphopenia (peripheral blood lymphocyte counts),
    • Severe infections,
    • Malignancies.
    • Pregnancies
    • Special situations (e.g. overdose)

    Measured: Through study completion, an average of 24 months

  14. Preventing loss of brain volume

    (MRI) Change over 24 months of the study in ventricular volume assessed using the VIENA technique.

    Measured: Screening, Month 6 and 24

  15. Preventing loss of brain volume

    (MRI) Change over 24 months in brain volume assessed using the "Structural Image Evaluation, using Normalisation, of Atrophy" (SIENA) technique

    Measured: Screening, Month 6 and 24

  16. Preventing loss of spinal cord cross sectional area

    (MRI) Change in the total cross-sectional area of spinal cord (at level C2) over 24 months

    Measured: Screening, Month 6 and 24

  17. Preventing new focal demyelinating lesions and T2 burden of disease increase.

    (MRI) Total number of new focal demyelinating brain lesions over 24 months

    Measured: Screening, Month 6 and 24

  18. Preventing new hypo-intense lesions ("black holes") on T1 weighted MRI

    (MRI) Total number of new hypo-intense T1 lesions over 24 months

    Measured: Screening, Month 6 and 24

  19. Degree of unblinding

    To determine the perception of treatment allocation for both participants and trial teams at 24 months.

    Measured: Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2021
  2. Study start25 Jun 2021
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
204 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04695080
Sponsor's protocol ID
258909
Other IDs
2018-005038-39, 2018
Acronym
ChariotMS
Status last verified
Sep 2026
First submitted
6 Nov 2020
Last updated
8 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Cladribine (MAVENCLAD®) in people with Advanced Multiple Sclerosis and Progressive Multiple Sclerosis, run by Queen Mary University of London at 22 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The 9-HPT peg speed (tasks/second) at 24 months (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04695080.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.

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