EAN 2023 | Octopus: a revolutionary multi-arm, multi-stage trial for progressive MS
Sean Apap Mangion, MD, UCL Queen Square Institute of Neurology, London, UK, discusses the first multi-arm, multistage (MAMS) trial for multiple sclerosis (MS), which has recently been launched in the UK. The Octopus trial will simultaneously test numerous agents in patients with primary and secondary progressive MS, where there is an urgent unmet need for effective treatment options. The use of a common standard of care group, as well as the ability to drop agents from the trial that do not show promise and replace with new trial arms, makes the design highly efficient, saving time, reducing costs, and limiting the number of patients not in an active intervention arm. Initially, Octopus will test metformin and alpha-lipoic acid, two drugs that have shown neuroprotective effects in preclinical studies. Dr Apap Mangion highlights plans to expand this revolutionary trial approach to other neurological conditions where novel therapeutics are of great need. This interview took place at the European Academy of Neurology (EAN) 2023 Congress in Budapest, Hungary.
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Transcript (edited for clarity)
Multi-arm, multi-stage trials involve assessing a number of different drugs against common treatments, so a standard of care typically, and they run sequentially, simultaneously going through different stages with the first stage typically being to assess their feasibility overall, somewhat akin to a Phase II trial. Then if they pass that initial assessment, they go on to a formal, longer assessment stage, which is the equivalent of a Phase III trial...
Multi-arm, multi-stage trials involve assessing a number of different drugs against common treatments, so a standard of care typically, and they run sequentially, simultaneously going through different stages with the first stage typically being to assess their feasibility overall, somewhat akin to a Phase II trial. Then if they pass that initial assessment, they go on to a formal, longer assessment stage, which is the equivalent of a Phase III trial. There’s a number of studies looking at it, but fundamentally it’s that you have significant savings involved with the setup of such a large trial, which is able to assess things on a continuous basis. So, we can tell that it’s beneficial both in terms of time and in terms of cost, as well as the individuals involved, so overall, you require quite a large amount of participants, you require quite a large initial cost and time effort in order to set it up. But, in the long term when you compare it to the equivalent number of trials that you’d need to assess a similar number of drugs, then actually you’re saving on all of those fronts.
So, Octopus is set up specifically for progressive forms of multiple sclerosis. As I’m sure most of the audience is aware, there’s a very limited number of treatments available for them and because of that, trying to set up a number of separate trials to assess different treatment methodologies, it’s just very inefficient. Octopus is starting off earlier this year testing two different drugs against standard of care, with the scope of adding more as time progresses. We’re going to be looking at primarily drugs which improve remyelination or neuroprotection in the first instance and will be through the first phase of the trial by mid-2024 hopefully.
At the moment it’s metformin from a remyelination perspective, there’s very convincing and supportive animal data which suggests that it improves oligodendrocyte function and remyelination. And the other is alpha lipoic acid, which has been investigated in a number of different countries for a variety of conditions, but again, there’s very encouraging animal studies and more recently even human trials showing that it can really improve brain atrophy rates, which is the interim outcome measure that we’re using for Octopus.
There’s a large effort across the UK to see if we can expand it across a number of different neurological conditions, primarily those involving neurodegeneration. So, there’s talks about setting it up for dementias, Parkinson’s disease, and motor neuron disease, which are all in various stages comparable to Octopus. We relied on the STAMPEDE trial and are working very closely with the MRC and Professor Max Palmer who had set that all up initially, and we form part of a whole group that are setting these trials up and moving them forward.
So, fundamentally they could reach out to UCL, to the MRC to see whether or not they could come on board. We have had a number of additional sites which have expressed an interest in joining us. In this instance, right now we’ve got 15 sites which are going to be coming online and taking part in the first phase of the trial, but multi-arm, multi-stage trials require a lot of participants, so anyone that would want to get involved could just reach out and I’m sure we can discuss it further.
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