Reducing the frequency of Autoimmune adverse events in the treatment of Multiple sclerosis with alemtuzumab using B-celL dEpletion (RAMBLE): a phase II, randomised, placebo-controlled clinical trial.

INTERVENTION: The investigational product is rituximab, which is a monoclonal antibody against CD20 that cause lysis of B‐lymphocytes. The antibody is a humanised mouse antibody and is administered intravenously via an infusion over 30 minutes. The dosage to be used is 100 mg/m2 of estimated body surface area (BSA). BSA will be estimated based on height and weight according to the Du Bois formula. Arm 1: Intervention Arm 2: Placebo CONDITION: Multiple Sclerosis; ; Multiple Sclerosis Neurological ‐ Multiple sclerosis PRIMARY OUTCOME: Frequency of autoimmune adverse events (time to event); ; Assessed via Monitoring visits , MRI scans, blood tests, liver function tests and urine tests ; ; [Time point: at 3 years post trial commencement (31/12/2024); ; Monitoring Visits (every 6 months) intercurrent illness, relapse history and concomitant medications, EDSS change, MSIS‐29 change; ; MRI every 12 months ‐ Looking for Number of new T2 MRI brain lesions, Number of new Gd‐enhancing lesions; ; FBC/lymphocyte subsets – lymphocyte subsets will be performed at weeks ‐1, 4, 9, 13, 26, 35, 50, 57, 61, 65, 78, 83 and 104. ‐ B cell subpopulation counts at theses times; ] SECONDARY OUTCOME: Monitoring Other adverse events ; [Time point: at 3 years post trial commencement (31/12/2024) ; ; Monitoring Visits (every 6 months) intercurrent illness, relapse history and concomitant medications, EDSS change, MSIS‐29 change ; ; MRI every 12 months ‐ Looking for Number of new T2 MRI brain lesions, Number of new Gd‐enhancing lesions ; ; FBC/lymphocyte subsets – lymphocyte subsets will be performed at weeks ‐1, 4, 9, 13, 26, 35, 50, 57, 61, 65, 78, 83 and 104. ‐ B cell subpopulation counts at theses times ; ] INCLUSION CRITERIA: ‐ Diagnosed with relapsing remitting MS (RRMS) by a neurologist ‐ Diagnosis of MS meeting 2017 McDonald criteria ‐ Diagnosed with MS within the previous 10 years ‐Expanded disability status scale (EDSS)15 score < 5.0 ‐English speaking or non‐English speaking who can ensure external interpreter assistance (e.g. relative or friend) to attend all visits for the duration of the clinical trial. ‐Available to attend clinic visits ‐Willing to sign up for and comply with Bloodwatch monitoring program