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

Background Disease modifying treatments (DMTs) have transformed the management of people with MS (pwMS). However, patients 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 relatively safe DMT. effectively depletes B cell subsets, particularly memory cells, potential key mechanism disease control pwMS. Aims To test efficacy, safety cost-effectiveness cladribine tablets (EDSS 6.5–8.5), expand mechanistic understanding provide evidence NHS adoption. Methods Randomised, double-blind, placebo-controlled phase IIb trial. The primary measure 9-hole peg speed at 104 weeks vs baseline. detect 15% treatment effect 9-HPT 90% power 5% significance 20% drop-out we calculated sample size n=200 across 20 UK sites. Conclusions ChariotMS will be first DMT-trial focussing pwAMS. If successful, would landscape include platform add-on therapies. start recruitment nationwide from 1 Sep 2020. [email protected]