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

NCT04695080 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 2589092018-005038-39
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 22

Brief 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% 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).

Conditions

Advanced Multiple Sclerosis; Progressive Multiple Sclerosis

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)

Outcome Measures

Primary Outcomes (2)

• 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.

  24 months

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

  24 months

Secondary Outcomes (19)

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

  Screening, Month 6, 12, 18 and 24

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

  Screening, Month 6, 12, 18 and 24

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

  Screening, Month 6, 12, 18 and 24

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

  Screening, Month 6, 12, 18 and 24

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

  Screening, Month 6, 12, 18 and 24

Other Outcomes (8)

• To determine if cladribine correlates with memory Bcell count.

  Screening, Month 12 and 24

• To determine association between Memory B cell count and 9HPT speed.

  Screening, Month 6, 12, 18 and 24

• To determine association between Memory B cell count and 9HPT speed.

  Screening, Month 6, 12, 18 and 24

Study Arms (2)

Cladribine (MAVENCLAD®)

ACTIVE COMPARATOR

Drug: Cladribine (MAVENCLAD®)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

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.

Cladribine (MAVENCLAD®)

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Queen Mary University of London: lead
• National Institute for Health Research, United Kingdom: collaborator
• Merck Serono Limited, UK: collaborator
• Multiple Sclerosis Society of Great Britain & Northern Ireland: collaborator
• National Multiple Sclerosis Society: collaborator
• Barts & The London NHS Trust: collaborator

Study Sites (22)

Queens University Belfast (Belfast Health and Social Care Trust)

Belfast, BT12 6BA, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham

Birmingham, B15 2TH, United Kingdom

Location

Cardiff University Hospital

Cardiff, CF14 4XW, United Kingdom

Location

University Hospitals of Coventry and Warwickshire NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

Anne Rowling Clinic, University of Edinburgh

Edinburgh, EH16 4SB, United Kingdom

Location

Queen Elizabeth University Hospital Glasgow

Glasgow, G51 4TF, United Kingdom

Location

University Hospital Hairmyres, NHS Lanarkshire

Glasgow, G75 8RG, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Walton Centre NHS Trust

Liverpool, L9 7LJ, United Kingdom

Location

Royal London Hospital

London, E1 1FR, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

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

London, RM7 0AG, United Kingdom

Location

Lewisham and Greenwich NHS Trust

London, SE13 6LH, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust

London, SW17 0RE, United Kingdom

Location

Luton and Dunstable Hospital

Luton, LU4 0DZ, United Kingdom

Location

Salford Royal Hospital NHS Trust

Manchester, M6 8HD, United Kingdom

Location

Aneurin Bevan University Health Board

Newport, NP20 2UB, United Kingdom

Location

Nottingham University Hospital (Nottingham University Hospitals NHS Trust)

Nottingham, NG7 2UH, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2JF, United Kingdom

Location

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Morriston Hospital, Swansea

Swansea, SA6 6NL, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Charcot-Marie-Tooth disease, Type 1F

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

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

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: January 5, 2021
• Study Start: June 25, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (22)