028 Cladribine to halt deterioration in people with advanced multiple sclerosis (ChariotMS)

Abstract

BackgroundDisease modifying treatments (DMTs) have transformed the management of people with MS (pwMS). However, patients with an EDSS>6.5 (pwAMS) are considered beyond DMT due to (i) focus on ambulation as outcome measure, (ii) assumption that in pwAMS inflammation plays no role, and(iii) disregard for potentially length-dependent neuro-axonal damage. Cladribine is a CNS penetrant, effective, convenient and relatively safe DMT. Cladribine effectively depletes B cell subsets, particularly memory B cells, a potential key mechanism of disease control in pwMS.AimsTo test the efficacy, safety and cost-effectiveness of cladribine tablets in pwAMS (EDSS 6.5–8.5), expand the mechanistic understanding of cladribine in pwAMS and provide evidence for NHS adoption.MethodsRandomised, double-blind, placebo-controlled phase IIb trial. The primary outcome measure is 9-hole peg test speed at 104 weeks vs baseline. To detect a 15% treatment effect in 9-HPT peg speed with 90% power at 5% significance and 20% drop-out we calculated a sample size of n=200 across 20 UK sites.ConclusionsChariotMS will be the first DMT-trial focussing on pwAMS. If successful, ChariotMS would expand the DMT landscape to include pwAMS and provide a platform for potential add-on therapies. ChariotMS is due to start recruitment nationwide from 1 Sep 2020.david.lieberman@nhs.net