Symposium Blogathon: Focus on… Clinical Trial Updates (part 1)

Symposium Blogathon: Focus on… Clinical Trial Updates (part 1)

Reading Time: 5 minutes

This blog is part of our Symposium Blogathon series – where we are counting down to the 33rd International Symposium. Numbers in bold blue type correspond to the code in the abstract book. Click on the number to be redirected to the full abstract.

Clinical trials are research studies in human volunteers that determine whether potential treatments are safe and effective. Clinical trials are usually conducted in four progressive phases which check for safety and efficacy, establish the correct dosage and method of delivery, and assess the drug’s ability to treat the condition it is designed for.

The number of ALS/MND clinical trials this year is reflected at the International Symposium on ALS/MND, with presentations on a wide variety of different potential treatments.

Over the next two blogs we take a closer look at the talks and posters from this year’s Symposium which will be providing updates on current clinical trials for potential new drugs for ALS/MND.


In her oral presentation (C2), Dr Elisabetta Pupillo will provide an overview of the results of the Phase 2 trial of RNS60. Inflammation in the brain and the spinal cord is thought to contribute to MND progression. RNS60 is hoped to have anti-inflammatory properties, to help reduce this inflammation, as well cytoprotective properties, meaning it could help to protect cells from harmful agents which may be linked to ALS/MND.

The Phase 2 trial was a 24-week randomised, double-blind, placebo-controlled trial. This means that the participants were randomly assigned to either the RNS60 treatment group or the placebo (dummy drug) group for 24-weeks, and neither the participants nor those running the trial knew who was in which group. The trials main aim was to see if treatment with RNS60 impacted a range of different potential biological markers of ALS/MND compared to the placebo. The trial also investigated the effect on function (through ALSFRS-R), survival and quality of life.


Inflammation in the brain and spinal cord is thought to contribute to MND progression. Our bodies can help to control inflammation through a type of immune system cell called a Regulatory T Cell (Treg). Research has shown that Interleukin-2 (IL-2) can help to control Tregs and low doses have been shown to increase the number and function of Treg cells in the blood. A previous clinical trial, called IMODALS, investigated the use of low doses of IL-2 in people living with MND. The trial showed that the number of circulating Tregs was increased in people living with MND. MIROCALS (Modifying Immune Response and OutComes in ALS) is an 18-month, randomised, double-blind, placebo-controlled clinical trial, investigating the use of low-dose IL-2 in people living with ALS/MND.

Blog | 16 March 2022 | Eleanor Green
Symposium Spotlight: A closer look at IMODALS clinical trial outcomes

In his presentation (C3), Dr Gilbert Bensimon will give an overview of this clinical trial, the study design and population. He will then present the top-line data looking at whether IL-2 was effective in treating ALS/MND and report on the safety analysis. This will include data the primary outcome, which was survival, and the major secondary outcome measures including ALSFRS-R.


RESCUE-ALS is a Phase 2 clinical trial investigating in people recently diagnosed with ALS/MND. CNM-Au8 is an aqueous suspension of gold nanocrystals which have been shown to enhance neuronal metabolic energy, reduce oxidative stress and improve protein homeostasis – all associated with the development with MND.

The trial was a 36-week randomised, double-blind, placebo-controlled trial and outcome measures of the trial included average motor unit index score (MUNIX, which estimates the number of motor neurone/muscle connections), ALSFRS-R score and survival. The top-line results of the trial were reported at the Symposium last year and although the overall results were negative, there were some promising trends, especially in survival benefit. After the 36-week randomised period, the participants entered the open-label extension of the trial. This is where all participants, regardless of whether they were randomised to treatment or the placebo, received the treatment. In his presentation titled ‘Evidence for a survival benefit in ALS with CNM-Au8 treatment: interim results from the RESCUE-ALS trial long-term open label extension’ (C4) Dr Steve Vucic will report on data from the open label extension, including survival data and safety analysis.


Tofersen is a type of potential treatment known as an antisense oligonucleotide (ASO) that targets the SOD1 genetic mutation thought to cause ALS/MND. The drug has been designed to work by stopping the production of abnormal SOD1 that is toxic to motor neurones. The results of the Phase 3 clinical trial, called VALOR, were reported at last year’s Symposium as late breaking news. The trial did not hit its primary endpoint of a significant difference in disease progression, as measured by the ALSFRS-R, between those on the treatment and those on placebo. However, there were positive trends observed in some other endpoints including a lowering of the amount of toxic SOD1 protein.

Earlier this year, the results of the first 6 months of the open label extension of the trial were announced. These results further highlighted the positive trends observed in the randomised part of the trial. The results showed that a potential biomarker (a biological fingerprint) of ALS/MND, called neurofilament light chain, was found to be reduced and stay reduced for 52-weeks for those who received Tofersen at the start of the trial. A survival benefit was also observed for those who received Tofersen at the start of the trial.


Blog | 10 June 2022 | Charlotte Roy
VALOR Biogen’s Tofersen trial: a look at the open label extension data

In his talk titled ‘Evaluating efficacy and safety of Tofersen in adults with SOD1-ALS: results from the Phase 3 VALOR trial and open-label extension’ (C5) Dr Tim Miller will give an overview of the results from the trial and the open-label extension, including results from additional exploratory endpoints.

HEALEY Platform Trial

The HEALEY platform trial aims to accelerate the process of finding an effective treatment for ALS/MND by testing multiple drugs in a simultaneous and adaptive manner. The trial also allows participants to have a greater chance of being on the treatment rather than placebo. Since the trial started, 5 drugs have been added: Zilucoplan, Verdiperstat, CNM-Au8, Pridopidine and Trehalose. Showing the adaptive nature of the trial, the Zilucoplan arm was stopped early as it showed no benefit in people living with ALS/MND.

Results from regimens B and C of the trial were announced earlier in the year. Unfortunately, both the Verdiperstat arm and the CMN-Au8 did not meet their primary endpoints. However, CMN-Au8 did show similar positive trends in survival benefit as those described above in the RESCUE-ALS trial. Further details of the results of all 4 regimens of the trial will be presented in a poster (CLT18) at this year’s Symposium.

Additionally, to the poster, team members behind the HEALEY platform trial will present the results from the trial in a session which will run parallel, on 9 December, to the main programme. To kick off the session Dr Merit Cudkowicz will give an overview of the Platform trial, including its aim and purpose. Dr Sabrina Paganoni, Dr Jinsy Andrews and Dr James Berry/Dr Nicholas Maragaskis will then present data from regimen A-C respectively. The session will close with Dr Cudkowicz discussing the current and future directions of the Platform trial.

Stay informed

If you have come across this blog through the Symposium website, or a general search please subscribe (see top right-hand corner of page) and you’ll be notified every time we upload a new article.

You can follow our research account on Twitter. We tweet about up to the minute research and will be tweeting throughout the Symposium using the hashtag #alsmndsymp.

Take a look at the schedule of blogs for November as we continue counting down to the 33rd International Symposium on ALS/MND with our Symposium Blogathon.

To listen to talks live, take part in the Q&As and visit the live poster sessions, register for the International Symposium now.

I work in the Research Development team as a Senior Research Information Co-ordinator. I graduated from the University of Nottingham with a PhD in Chemistry in 2020. After finishing my PhD, I joined an R&D company based in Nottingham where I spent my time synthesising potential new drug treatments for a wide variety of diseases. As part of my role I will help the team communicate the latest MND research on this blog, as well as on our twitter page (@MNDResearch).