Clinical trial of anti-Epstein-Barr virus therapies for the prevention of progression in multiple sclerosis

Stage 1 - Co-primary endopoint of frequency of salivery EBV DNA detection in monthly samples and serum EBNA1 antibody titres in serum;; Stage 2 - Time to 6 month confirmed disability progression (CDP) using a composite of expanded disability status scale (EDSS), Timed 25-Foot Walk (T25FW) and 9-Hole Pet Test (9-HPT)

Multiple sclerosis (MS) is a potentially devastating disease of the central nervous system and progressive MS, which occurs in up to two-thirds is the most severe form. Current therapies for MS have limited effect in the progressive stage. Recent studies have confirmed that the primary cause of MS is latent infection with Epstein-Barr virus (EBV). We have conducted a systematic review of existing drugs with potential anti-EBV effects. Through an internationally peer reviewed process we have selected two promising agents with known acceptable safety profiles and proven efficacy against EBV. In order to maximise efficiency to find the best such treatment we have partnered with experts in the UK in designing a state of the art trial to test these agents in progressive MS. We propose to run an innovative adaptive phase III clinical trial to evaluate the effectiveness of promising anti-EBV therapies for progressive MS by repurposing old drugs (Spironolactone and Famciclovir) for a new indication. In stage 1 we will compare the effect of the two agents against dummy-treatment (placebo) in their ability to reduce antibodies to EBV and the amount of EBV shed in saliva in relatively small numbers (total 150) over 6 months. The agent that produces the largest reduction in these measures will then progress to state 2, where the clinical effectiveness of this treatment will be compared to placebo over a period of 3 years in a larger group (total 300). This study will facilitate the participation of Australians with progressive MS in a novel trial of anti-EBV therapies. If the outcomes of this study are positive then the impacts would be immense. It has been noted that the lack of treatment for progressive forms of MS is the single greatest unmet need for people with MS. The advent of an effective therapy to prevent further progression or even improvement would be a huge step forward. There would be similar implications for the wider MS community.