Home › Trials › NCT04695080

Using Cladribine to Improve Function in Advanced Multiple Sclerosis

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?

PHASE2; PHASE3 · Queen Mary University of London · NCT04695080

This study is testing if the medication Cladribine can help improve movement and daily function in adults with advanced multiple sclerosis.

Quick facts

PhasePHASE2; PHASE3
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years and up
SexAll
SponsorQueen Mary University of London (other)
Drugs / interventionsnatalizumab, alemtuzumab, rituximab, ocrelizumab, ublitiuximab, ofatumumab, methotrexate, cyclophosphamide
Locations22 sites (Belfast and 21 other locations)
Trial IDNCT04695080 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of Cladribine (MAVENCLAD®) in patients with advanced multiple sclerosis (MS) to assess its safety, efficacy, and cost-effectiveness. The study is a multi-centre, randomized, double-blind, placebo-controlled trial involving participants aged 18 and older with an Expanded Disability Status Scale (EDSS) score between 6.5 and 8.5. Participants will receive Cladribine or a placebo over a 24-month period, with a focus on evaluating improvements in upper limb function and overall disease progression. The trial aims to provide a convenient and effective treatment option for individuals with significant disability due to MS.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced multiple sclerosis and an EDSS score between 6.5 and 8.5.

Not a fit: Patients with known hypersensitivity to Cladribine or those with uncontrolled diabetes, hypertension, or hypercholesterolemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve upper limb function and halt disease progression in patients with advanced multiple sclerosis.

How similar studies have performed: Other studies have shown promising results with Cladribine in treating relapsing forms of multiple sclerosis, but this specific application in advanced MS is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion criteria:

1. pwAMS aged 18+ years with an EDSS of 6.5-8.5 (inclusive)
2. 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/.
3. 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.
4. Confirmation of MS diagnosis according to the McDonald Criteria (2017) Thompson et al. 2018).
5. In the judgement of the investigator, evidence of deterioration of upper limb function during the 2 years running up to the screening date.

Exclusion Criteria

1. Participants with known hypersensitivity to Cladribine of any grade (as per CTCAE grading system) should be excluded
2. Any uncontrolled diabetes, arterial hypertension and hypercholesterolaemia as determined by PI or delegated sub-investigator
3. A history of stroke, deep vein or sinus venous thrombosis (including pulmonary embolus) and/or myocardial infarction
4. Moderate to severe renal impairment (creatinine clearance \<60 ml/min)
5. Moderate to severe hepatic impairment (Child-Pugh score \>6)
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.
7. Pregnancy including planning to father a child or breastfeeding
8. Body weight less \<40kg
9. 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
10. Acute infection (uncontrolled)
11. Infection with Human Immunodeficiency Virus 1 and/or 2
12. 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.
13. Precancerous condition
14. Total lymphocyte count \<1.0\*109/L
15. 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.
16. Relapse within six months before screening
17. 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.
18. 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.
19. Treatment with any interferon-beta, glatiramer acetate, teriflunomide or dimethyl-fumarate within three months before screening.
20. Treatment with natalizumab, fingolimod, siponimod, ponesimod, ozanimod (or other Sphingosine-1-phosphate receptor modulators) within three months of screening.
21. Treatment with azathioprine, methotrexate, or cyclosporine within six months before screening.
22. pwAMS treated with teriflunomide will need to undergo accelerated elimination of the compound before being considered (Research and Case Medical Research 2019).
23. 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.
24. Treatment with fampridine: If they are already on treatment for at least six months, 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.
25. Concurrent participation or previous participation within the last 6 months in another clinical trial of an IMP or medical device.
26. Unable to swallow tablets

Where this trial is running

Belfast and 21 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Advanced Multiple Sclerosis, Progressive Multiple Sclerosis, Multiple Sclerosis, Progressive multiple sclerosis, Advanced multiple sclerosis, Upper limb function, Cladribine, Quality of life

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.