ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis
- Conditions
- Progressive Multiple SclerosisAdvanced Multiple Sclerosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT04695080
- Lead Sponsor
- Queen Mary University of London
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cladribine (MAVENCLAD®) Cladribine (MAVENCLAD®) - Placebo Placebo -
- Primary Outcome Measures
Name Time Method The 9-HPT peg speed (tasks/second) at 24 months 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.9-HPT proportion of patients who do not deteriorate at 24 months 24 months
- Secondary Outcome Measures
Name Time Method Preventing loss of brain volume Screening, Month 6 and 24 (MRI) Change over 24 months in brain volume assessed using the "Structural Image Evaluation, using Normalisation, of Atrophy" (SIENA) technique
Preventing new focal demyelinating lesions and T2 burden of disease increase. Screening, Month 6 and 24 (MRI) Total number of new focal demyelinating brain lesions over 24 months
Preventing new hypo-intense lesions ("black holes") on T1 weighted MRI Screening, Month 6 and 24 (MRI) Total number of new hypo-intense T1 lesions over 24 months
Change over 24 months of the study in clinical outcome measure: ARAT Screening, Month 6, 12, 18 and 24 ARAT (Upper Limb Function Test) upper limb function test score
Change over 24 months of the study in clinical outcome measure: EDSS Screening, Month 6, 12, 18 and 24 The proportion of the cladribine versus placebo arms with an increase of \>=0.5 in EDSS score over 24 months.
Change over 24 months of the study in clinical outcome measure: SLCVA Screening, Month 6, 12, 18 and 24 SLCVA (Sloan low contrast letter visual acuity) score.
Change over 24 months of the study in clinical outcome measure: NFI-MS Screening, Month 6, 12, 18 and 24 NFI-MS (Neurological Fatigue Index-Multiple Sclerosis) score.
Change over 24 months of the study in clinical outcome measure: MSIS-29v2 Screening, , Month 6, 12, 18 and 24 MSIS-29v2 (Multiple Sclerosis Impact Scale) quality of life score
Change over 24 months of the study in clinical outcome measure: SDMT Screening, Month 6, 12, 18 and 24 SDMT (The Symbol Digit Modalities Test) score.
Safety/occurrence of adverse events Through study completion, an average of 24 months Safety:
* Any AEs/SAEs,
* Lymphopenia (peripheral blood lymphocyte counts),
* Severe infections,
* Malignancies.
* Pregnancies
* Special situations (e.g. overdose)Preventing loss of spinal cord cross sectional area Screening, Month 6 and 24 (MRI) Change in the total cross-sectional area of spinal cord (at level C2) over 24 months
Change over 24 months of the study in clinical outcome measure: ABILHAND Screening, Month 6, 12, 18 and 24 ABILHAND score for manual ability
Change over 24 months of the study in clinical outcome measure: T25ftWT Screening, Month 6, 12, 18 and 24 Lower Limb Function: The T25ftWT (Timed 25 foot walk test) will be collected in all pwAMS able to walk the required distance twice.
Change over 24 months of the study in clinical outcome measure: WPAI-GH Baseline, Month 6, 12, 18 and 24 WPAI-GH (Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI:GH) score
Degree of unblinding Month 24 To determine the perception of treatment allocation for both participants and trial teams at 24 months.
Change over 24 months of the study in clinical outcome measure: EuroQoL EQ-5D-5L Screening, Month 6, 12, 18 and 24 Cost-utility: health and social care and other costs.
Trial Locations
- Locations (22)
Morriston Hospital, Swansea
🇬🇧Swansea, United Kingdom
Luton and Dunstable Hospital
🇬🇧Luton, United Kingdom
Salford Royal Hospital NHS Trust
🇬🇧Manchester, United Kingdom
Queens University Belfast (Belfast Health and Social Care Trust)
🇬🇧Belfast, United Kingdom
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, United Kingdom
University Hospitals of Coventry and Warwickshire NHS Trust
🇬🇧Coventry, United Kingdom
Cardiff University Hospital
🇬🇧Cardiff, United Kingdom
Anne Rowling Clinic, University of Edinburgh
🇬🇧Edinburgh, United Kingdom
Queen Elizabeth University Hospital Glasgow
🇬🇧Glasgow, United Kingdom
University Hospital Hairmyres, NHS Lanarkshire
🇬🇧Glasgow, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
Walton Centre NHS Trust
🇬🇧Liverpool, United Kingdom
Queen's Hospital (Havering and Redbridge University Hospitals NHS Trust)
🇬🇧London, United Kingdom
Lewisham and Greenwich NHS Trust
🇬🇧London, United Kingdom
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Aneurin Bevan University Health Board
🇬🇧Newport, United Kingdom
University Hospitals of North Midlands NHS Trust
🇬🇧Stoke-on-Trent, United Kingdom
University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
Nottingham University Hospital (Nottingham University Hospitals NHS Trust)
🇬🇧Nottingham, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom