'25 at 25': OCTOPUS – speeding up new treatments for progressive MS

19 Aug 2024

OCTOPUS is the first ever multi-arm multi-stage (MAMS) clinical trial in multiple sclerosis (MS). As part of our ’25 at 25’ series, we explore how the trial aims to transform the way that new treatments for MS are tested, with the potential to deliver life-changing treatments up to three times faster than a traditional clinical trial.

MS is a neurodegenerative condition caused by the immune system attacking the protective lining (myelin) that covers nerves in the brain and spinal cord. This can result in a range of symptoms, including problems with balance and walking, vision, numbness and tingling, pain, tremor, fatigue, and difficulties with memory, thinking and talking.

MS affects around 135,000 people in the UK and 2.9 million people globally. It is one of the most common causes of disability in young adults.

There are two main types of MS. People with relapsing-remitting MS have distinct attacks of symptoms which then fade away partially or completely. But for people with progressive MS, there are no distinct attacks. Instead, symptoms and disability get gradually worse over time.

Progressive MS is often ‘secondary’, where it starts to gradually worsen after a period of relapsing-remitting MS. Less commonly, progressive MS can be ‘primary', where symptoms and disability gradually worsen from the beginning of diagnosis.

While there is no cure for MS, people with relapsing-remitting MS have access to many ‘disease modifying therapies’ (DMTs). These drugs can reduce the frequency and intensity of relapses. They can also slow down the damage to nerves caused by MS, which builds up over time.

Unfortunately, these drugs do not have the same effect in progressive MS. People with progressive MS can manage their symptoms, but there are very few treatments that can slow or prevent their disease worsening. They also have a limited effect. OCTOPUS aims to change this.

The trial is testing promising medications which could protect the nerves from the immune system’s attack, or repair damage already done.

Discussions around OCTOPUS began as early as 2016 as part of the UK MS Society’s Clinical Trials Network. This involved many partners, including those from the Queen Square Institute of Neurology (IoN), UCL. The MRC CTU at UCL got involved in 2019, bringing along expertise in the design, conduct and analysis of MAMS trials. The trial is funded by the MS Society.

MAMS trials like OCTOPUS test multiple experimental treatments at the same time, all compared to a single control arm. Data will be analysed while the trial is ongoing, in an ‘interim analysis’. Treatments which show enough promise will then seamlessly progress to the next stage of the trial, while the other treatments will be dropped. More treatments can be added as new contenders emerge.

This is much more streamlined than running a separate trial for each individual treatment. Therefore, a MAMS trial can help make new treatments available for people with progressive MS much sooner.

People living with MS played an important role in deciding how and which treatments should be tested in OCTOPUS. Sitting on a panel alongside world-renowned scientists and clinicians, MS participant representatives reviewed and ranked potential treatments put forward by the research community. Together, they whittled the list down from over 100 potential drugs.

To help make the process more efficient, there was a particular focus on ‘repurposed’ drugs, meaning they are already used in other conditions. Researchers already know that these drugs are safe and have an idea of the possible side effects. This means that OCTOPUS can focus more quickly on whether these treatments are effective at treating progressive MS.

OCTOPUS opened in 2023. Alongside a placebo control arm, the trial is currently testing two repurposed drugs:

Metformin – a drug currently licensed to treat type 2 diabetes, which may also help repair the damaged lining of nerves in progressive MS.
Alpha lipoic acid – a food supplement which acts as an antioxidant, and has already been licensed in Germany to treat weakness, pain, numbness and tingling in damaged nerves.

More treatments, which may be repurposed or brand new, will join the trial in future.

OCTOPUS is now recruiting participants throughout the UK, with the aim to recruit 375 participants in the first analysis stage. The second analysis stage will bring the total up to around 1,200. Adults aged 70 or under, with either primary or secondary progressive MS, can take part.

In the first analysis stage, researchers will assess whether the study treatments can slow the rate at which the brain shrinks. Research has shown that slowing down brain shrinkage in MS is linked to slowing down disability. If a treatment does not show sufficient benefit, then the arm will be stopped. Results from the first analysis stage of OCTOPUS are expected in late 2026.

In the second analysis stage, researchers will directly assess those treatments which proceeded from analysis stage 1, to find out whether they can effectively slow or stop the progression of disability. This is the most important outcome for people living with progressive MS.

After a six month ‘wash-out’ period to get any remaining drug out of their system, participants who are on a treatment that is stopped in the first analysis stage will get the option to re-enter the trial in a different arm, if they are still eligible. This was another feature of the trial which came from the OCTOPUS participant representatives.

The response to this innovative and ambitious trial has been enormous, and recruitment to the first analysis stage of the trial continues to exceed expectations.

An extension to the OCTOPUS trial is also in development in Australia. PLATYPUS is funded by MS Australia and MS Western Australia (MSWA). The national sponsor is Griffith University, who will work closely with the MRC CTU at UCL to co-ordinate the trial. PLATYPUS aims to start in early 2025.

The MS community have been central to the design and running of OCTOPUS – from deciding which drugs to test down to choosing the trial’s name and logo. Following many years with few treatments, OCTOPUS and PLATYPUS now offer something powerful for people living with progressive MS: hope.

Further information: