One of the readers asked about anti-EBV trials and I would say there are loads of them and this one from Oz popped up like some social media listening and sending device. Personally I think these “we are doing a trial” papers are a waste of space but ProfK is doing them for chariotMS and AttackMS. Whilst I say good luck to them, one has to ask on what basis is this trial designed?
They say
What is already known on this topic
- Epstein-Barr virus (EBV) is a primary driver of multiple sclerosis (MS) pathology and may contribute significantly to disease progression. There are existing drugs with evidence for anti-EBV effects which may be repurposed for this indication.
What this study adds
- People with progressive MS do not have time to await development of new therapeutics to slow progression. STOP-MS has the potential to rapidly deliver evidence for effective anti-EBV therapies for this group. Em lets throw all we have at an unmet need and this is progressive MS
How this study might affect research practice or policy
- A positive result from the STOP-MS trial could be rapidly translated to clinical practice through applications for additional indications to regulatory authorities for these already approved therapies and through publication of clinical guidelines. Yep but what will a negative trial do to EBVresearch? So it is important to maximise the chance of success.
We are led to believe that EBV is the cause so we doing the trial in people who already have EBV? This the hard ask. OK you say it is an active central driver so why do the trial in progressive MS when there is a graveyard of trials as it has a tortuous design. Do we think that we kill the virus and it stops progression set in motion in an instant when no current treatments does this. The trial aims to assess two drugs to see if they block virus reactivation if they don’t they will look for ones that do before going on to the clinical stage. This study looks at one antiviral which has been used by ProfK during early studies with cladribine to limit anti-viral activity during immunosuppression.
Ward K, Li V, Ramanathan S, Hall LA, Buzzard K, Young K, Mckay F, Vigar V, Oishi S, Madrid San Martin L, Kaskow B, Parnell G, Campbell JA, Sun J, Smith C, Jokubaitis V, Kalincik T, Tscharke D, Potter A, Brady E, Lechner-Scott J, Steinman L, Parmar M, Chataway J, Hardy T, Carroll WM, Barnett MH, Taylor BV, Broadley SA; Australian Multiple Sclerosis Clinical Trials Consortium. Study protocol for a multicentre, randomised, double-blinded, placebo-controlled, multi-arm, multi-stage, trial of Spironolactone and famciclOvir in the treatment of Progressive Multiple Sclerosis to prevent disability progression: the STOP-MS trial. BMJ Neurol Open. 2025 Dec 23;7(2):e001313.
Introduction: Targeting progressive multiple sclerosis (MS) addresses the current single biggest unmet need in the MS therapeutic landscape and anti-Epstein-Barr virus (EBV) therapy potentially strikes at the root cause. The Spironolactone and famciclOvir in the treatment of Progressive MS to prevent disability progression (STOP-MS) trial has been developed to assess anti-EBV therapies in the treatment of progressive MS.
Methods and analysis: STOP-MS is a multi-arm, multi-stage, randomised, double-blind, placebo-controlled trial testing spironolactone and famciclovir to prevent disability progression in MS. Australians with progressive forms of MS, aged 25 to 70 years with established disability, are eligible. Recruitment commenced in March 2025 and the first participant was enrolled on 15 April 2025. The sample size for STOP-MS is 150 in stage 1 and 300 in stage 2. In stage 1, the composite primary outcome measures will be reduction of EBV DNA in saliva and serum EBV nuclear antigen-1 antibody titres. Minimum criteria for consideration of progression to stage 2 will be a 10% reduction in the composite outcome measure. In stage 2, the primary outcome measure will be 6-month confirmed disability progression analysed using Cox-proportional hazards.
Trial registration number: The STOP-MS trial has been acknowledged by the Therapeutics Goods Administration under the Clinical Trial Notification scheme (CT-2023-CTN-03 505-1) and is registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623000849695).
Source: multiple-sclerosis-research.org