SIZOMUS randomized clinical trial is on the roll

S
SIZOMUS anti-plasma cell RCT

I’m happy to notify that SIZOMUS (Safety of IxaZOmib targeting plasma cells in Multiple Sclerosis) is re-commencing after MHRA approval. This follows a pre-planned interim safety analysis.

MHRA stands for Medicines & Healthcare products Regulatory Agency and without their say so this trial would not have been able to proceed.

The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptably safe.

Why were the MHRA involved in SIZOMUS?

Ixazomib, the active agent in the study, although licensed for use in humans has not been tested in Multiple Sclerosis, nor it’s MOA (mode of action – cleaning the brain of plasma cells; the main source of antibodies in inflammatory disorders) studied in MS.

So of course, 5 participants (3 on active treatment; 2 on placebo) entered the study last year and took the drug for three months, and owing to lack of any significant side effects or serious adverse events the trial has now been given the go ahead to start full recruitment.

The running and safety of the clinical trial is overseen by the clinical trial committee. This committee is a star studded cast with many years of experience in MS and clinical trials:

  • Chair: Dr Rachel Farrell, Consultant Neurologist, National Hospital for Neurology & Neurosurgery
  • Second: Dr Wallace Brownlee, Consultant Neurologist, National Hospital for Neurology & Neurosurgery
  • Observer: Professor Gavin Giovannoni, Professor of Neurology, Barts Health NHS Trust
  • Lay representative: Mrs Catriona Whyte, MS Specialist Nurse, Essex Partnership University NHS Foundation Trust
  • Statistician: Dr Jonathan Bestwick, Senior Lecturer, Wolfson Institute of Preventative Medicine, Queen Mary University of London
  • Secretary: Miss Thamanna Begum, MS coordinator, Barts Health NHS Trust
  • Governance: Mrs Sabiha Khan, Department of Research & Governanace, Queen Mary University of London

It has taken 4 years to get this clinical trial off the ground, some of the delay not surprisingly has been due to COVID-19. However, we are happy to have this now officially off the ground and excited to see the fruition of many years of concept work that is finally seeing the light of day.

MD (Mouse Doctor) has been integral to the scientific development of this project and I’m sure he is anxious to see the initial outcomes of the clinical trial!

RUN SIZOMUS RUN! – The MS-Blog (multiple-sclerosis-research.org)

The 1st anti-plasma cell drug in MS. What should you ask? – The MS-Blog (multiple-sclerosis-research.org)

Do you want a cure? – The MS-Blog (multiple-sclerosis-research.org)

6.-PIS-v2.0-27Mar19-SIZOMUS-CLEAN

If you are interested in participation in the SIZOMUS study or would like to know more, please contact:
Dr. Mohammad Abouwafa (Wafa), Clinical Research Fellow for SIZOMUS; mohammad.aboulwafaali@nhs.net

Disclaimer: Please note that the opinions expressed here are those of the author NDG and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary University of London.

About the author

Neuro Doc Gnanapavan

13 comments

  • Very excited for this trial and it’s potential for the future!

    I consider myself to have ‘smouldering’ MS and am currently on the MS-STAT2 trial. I would be willing to volunteer for this trial but understand it’s one or the other, do you think this treatment has more potential for long-term affect on my progression?

    Thank you!

    • If you can flush out the plasma cells from their niches in the brain, then potentially a cure!!! But let’s not jump the gun here.

  • GO! GO! GO!!!! Thanks to you and to the first volunteers that enrolled in the trial!

    Do you plan to share preliminary one year data or we need to wait for the competition of the study? Are there other review steps until completion?

    • No other safety reviews planned (fingers x) – the MHRA are happy. We’ll be cracking on to the end. Sometimes interim analyses compromise the power of the study, which is the main reason.

      • Thank you for replying. Let’s hope the trial enrolls super fast!
        Can you elaborate on the fact that interim analysis compromise the power of the study? Do you mean that later evaluation may be influenced by prior results?

        • I’ve cut and paste this statement from a text on this, but unless pre-planned statistically affects the findings at the end:
          An interim analysis may be designed into a prospective trial at a predetermined point for many reasons. There may be a substantial question of whether the tested treatment may work, or whether it is safe. A decision to continue the study or to terminate it prematurely may result. Prospective planning is necessary because an interim analysis does affect power calculations, and the sample size may need to be increased if an interim analysis is planned. A decision to terminate a study may result when the interim analysis shows no treatment effect and it is unlikely that additional accrual will change the result. Such business decisions are unfortunate from a scientific perspective. Much more common is a decision to terminate a study because the interim analysis shows a statistically significant treatment result sooner than anticipated

          • So this trial could actually be completed in less than 2 years if we see a statically positive result with the interim analyses ?

  • So exciting to hear this trial is getting underway. Love the 2:1 arms with most people on treatment 🙂

    Reading up on ixazomid (as knew next to nothing about it) on datasheet: 99% protein bound and ‘Following oral administration, a tissue distribution study in rats revealed that the brain and spinal cord were amongst the tissues with the lowest levels, suggesting that the penetration of ixazomib through the blood-brain barrier appears to be limited’.

    Wondered what happens in humans? Thanks to whoever posted this link on previous post by Dr Wafa:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453381/

    Perhaps a little goes a long way!

    Good luck team SIZOMUS and all trial participants 🙂

    • Thanks 😊
      Yes, it does get in the brain, you have to note in tumours and in MS their is a leaky blood brain barrier that can lead to larger concentrations in the brain. Also, if the plasma cells are coming in from the periphery they may also take a hit, not to mention to mention the ones in the bone marrow- so a little goes a long way…

      • I remember that beside doing the post I did also some rough calculation and brain concentration measured is quite higher than IC50. But my calculations are for sure an approximation as I am no expert in the field. On the other hand, if everything was correct then we don’t have a little, we have enough. I was a bit baffled by the fact that I could not find literature data on the decrease of IgG levels on proteasome inhibitor treatment 🙁 that would be a great indicator as peripheral IgG decrease could be a worst case of central decrease of IgG

  • If you have had your NFL level tested for potential use of cladribine and it was clear so you are not eligible for cladribine would your ocb have been tested? Also are wheelchair users eligible for his trial?

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