World-first MS mega-trial opens

A world-first mega-trial for people living with progressive forms of multiple sclerosis (MS) has opened for participants in the UK, with UCLH the first of up to 30 sites across the country to begin recruiting patients the trial.

The MS Society funded trial, Octopus, is being led by researchers from the Queen Square MS Centre and MRC Clinical Trials Unit at University College London (UCL). The multi-arm, multi-stage (MAMS) platform trial is designed to transform the way treatments for progressive MS are tested – and will work up to three times faster than traditional trials. The same approach has changed how men with prostate cancer around the world are treated, answering eight research questions about treatments in just 15 years, rather than the 50 years or so it would have taken using a traditional trial design.

More than 130,000 people live with MS in the UK, and tens of thousands who have the progressive forms* have little to stop their MS getting worse. Disability progression is caused by degeneration of nerves in the brain – something that happens to all of us as we age, but more quickly in MS and other neurodegenerative conditions, like Alzheimer’s and Parkinson’s. Yet there are no treatments that target this.

Over several years, a group of world renowned scientific and clinical experts, as well as people living with MS, reviewed and ranked potential treatments. Their focus was on existing drugs used in other conditions that have the potential to protect nerves. The top two candidates, R/S alpha lipoic acid and metformin, were selected by the trial team as the first two drugs to test in the ‘arms’ of Octopus.

Participants are now being recruited at the University College London Hospitals NHS Foundation Trust (UCLH), where the trial is being supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre. There will eventually be up to 30 sites around the UK, including in Scotland, Wales, Northern Ireland, Yorkshire, the West Midlands and the South of England.

Ailsa Guidi, who is 47 and from Surrey, is one of the first participants on the Octopus trial and is a participant at UCLH. She was diagnosed with relapsing MS in 1999 when she was 24. She was told at the start of last year her MS had progressed to secondary progressive MS. Her mobility has been affected and she lives with daily fatigue.

Ailsa – who has three children and is medically retired – says: “When I was diagnosed with MS the doctors were keen to start me on a disease modifying therapy (DMT) straight away. But in 2015 I had a relapse which I didn’t get better from. Ever since my mobility has been permanently affected. It’s better or worse depending on the day, but I always use a walking aid, a two-wheel walker or a wheelchair. I also have an electric trike I use to go for a walk.

“In February 2022 my neurologist told me my MS had progressed to secondary progressive MS – something I knew was coming as my MS had got worse but I didn’t really want to hear. There are two treatments available that can help some people with secondary progressive MS but I’m sadly not eligible for them. I'm a positive person but facing progressive MS feels quite different from living with the relapsing form.

“It’s a strange thing to say, but a family friend said to me ‘it’s a good time to have MS as there’s so much happening in research’ and they’re right! My husband read about the Octopus trial in an MS Society newsletter last year. I said I had enough to focus on just managing my MS to sign up and asked him to instead! Since then, and after being accepted last month, I feel excited that I’m joining a long line of people who have helped progress MS research. Octopus has the potential to find treatments for people, like me, living with progressive MS – it’s given me hope.”

Dr Emma Gray, Assistant Director of Research at the MS Society, says: “Launching the world’s first multi-arm multi-stage trial for MS has long been an ambition of ours and opening the doors to Octopus is a momentous milestone. More than 130,000 people live with MS in the UK and there are tens of thousands with progressive forms who have nothing to stop their MS getting worse. By tapping into the potential of approved drugs, which may have the potential to protect nerves, we can develop new treatments for MS faster.

“This is a major moment for MS research – Octopus has the potential to change the clinical trials landscape around the world. It's thanks to all the wonderful participants like Ailsa that trials, like Octopus, can happen. We encourage people to explore the MS research possibilities available to them by going to www.mssociety.org.uk. We won’t stop until we have treatments that transform the lives of everyone with MS.”

Octopus is being led by leading neurologist at UCLH and UCL Professor Jeremy Chataway, whose vision to rethink trials for progressive MS was born over a decade ago. He said: “The multi-arm, multi-stage approach to trialling emerging medications has been utterly transformative in other conditions, so I’m thrilled we’re now able to apply it to progressive MS. Ultimately, Octopus will lead to more treatments for progression becoming available to people living with MS sooner.

“Getting to this stage has been an incredible joint effort of people up and down the country. The other large trial I am the Chief Investigator for, MS-STAT2, has shown we can run large-scale, nationwide trials for progressive MS. Now we're taking it to the next level, as we start a new journey to develop treatments for progressive MS. I know our amazing community of people is poised to help us make it to the top, so we can find the answers we so desperately need.”

Professor Max Parmar is the Director of the Medical Research Council Clinical Trials Unit at University College London. He led the development of the multi-arm, multi-stage approach to clinical trials and carried out the first major trial using this design, STAMPEDE, which was for prostate cancer. He is the co-lead of Octopus and says: “When the MS Society asked me to help create one of the first ever multi-arm multi-stage trials for a neurological condition, I was up for the challenge. Octopus will use the innovative aspects of STAMPEDE plus some even more advanced features.

“The key thing about STAMPEDE is that we’re getting answers to our questions decades faster than we would with any other approach. To find treatments for everyone with MS, we need trials to be as inclusive as possible and produce results much faster. This is what we want Octopus to achieve.”

Octopus is being funded by donations to the MS Society’s Stop MS Appeal. Stop MS needs to raise another £30 million of its £100 million target to help find treatments that could slow or stop the build-up of disability for everyone with MS.

Anyone who has primary or secondary progressive MS in the UK can register their interest via the UK MS Register. Visit www.ukmsregister.org/octopus

*Approximately 85% of people with MS are diagnosed with the relapsing form, where symptoms come in sudden attacks then fade. Two in three of them will go on to develop secondary progressive MS, where there is no remission and you become increasingly disabled. 10-15% of people have primary progressive MS, where symptoms gradually get worse from the outset.

Image: Dr Sean Apap Mangion, one of the researchers in the OCTOPUS trial team at UCLH, with patient Ailsa Guidi. Credit: MS Society