A few years back Prof G, whilst talking about MS at a conference was approached by Takeda Pharmaceuticals on whether we would be interested in targeting plasma cells; probably one of the last frontiers in MS. The ideas started spinning from there. Roll forward a few years, after meeting the necessary regulatory and institutional requirements, there is finally light at the end of the tunnel. NDG, Prof G, and the whole SIZOMUS team now stand at the frontiers of new science in MS. It has been a team effort, and together with supportive colleagues and patients, the study is hitting its first safety review in May. The first five participants (anon.) who started SIZOMUS in September have been key to this. We are forever hopeful that many more will benefit from this work years to come.
So what SIZOMUS clinical Trial is about?
SIZOMUS is a short name for “Safety of IxaZOmib targeting plasma cells in Multiple Sclerosis”.
This is a clinical trial to investigate for the first time the role of “anti-plasma cell” therapy in multiple sclerosis. It is a Phase 1b clinical study, which means it is concerned with the safety of using anti-plasma cell treatments in multiple sclerosis patients. Ixazomib (trade name Ninlaro) is a 2nd generation proteasome inhibitor. It triggers the apoptosis (programmed cell death) of cancer cells including malignant plasma cells (called multiple myeloma).
Why we should target Plasma cells in MS?
One of the main characters in the MS story is the presence of “antibodies”. These antibodies are key players in immune attack against different foreign agents such as bacteria and viruses and it is well known that plasma cells are the main factory for producing such antibodies.
In MS some of these plasma cells have been shown to relocate their domain to the brain and spinal cord, where they persist in their antibody production causing slow burn inflammation. However, most of the available artillery for MS do nothing to plasma cells; of course a plasma cell “can be” affected when you target its predecessor, the B cell but otherwise they are pretty much resilient. Plasma cells can survive for long-time once developed and continue to exert ongoing damage unless you specifically target them.
SIZOMUS study is the first of its kind to pave the way in answering the question of whether targeting these plasma cells will improve outcomes and hopefully reach the unmet need of stopping disease progression at the end.
Ready steady go! How can I participate?
If you are living in the UK with a diagnosis of MS and you are between 18-65 years of age, this is sufficient to contact the study and check for your eligibility further.
We will make sure that you are:
- Stable on your MS treatment (DMT, disease modifying treatment) if you have the relapsing-remitting form of MS (RRMS)
- Not on any DMT if you have the progressive form of MS (PMS)
- Have a CSF sample from a lumbar puncture (LP) which shows the presence of OCB, if you never done it before, we will repeat the LP at the screening visit of the study
- Agree to use contraception
- Be willing and able to provide written informed consent to participate
- Agree to comply with the requirements of the study protocol
- Be reasonably fit and able to attend study visits.
Also, we will make sure that you do not have any of the following:
- Have had a MS relapse within the last month
- Be pregnant or breastfeeding
- Have had recent major surgery
- Have a serious infection at the time of the screening visit, or a history of HIV, hepatitis, tuberculosis or syphilis infections
- Have any other serious medical or psychiatric condition, which in the doctor’s opinion may make it inappropriate for you to take part. This includes certain cancers, uncontrolled heart conditions and any other neurological disease apart from MS.
What does Taking part involve?
The study consists of anumber of steps taking place at the Royal London Hospital.
- Screening and baseline phase (lasting up to 8 weeks)
During this phase we will make sure that you meet all the eligibility requirements mentioned above through clinical assessment as well as many tests and procedures.
- Treatment phase (from the first dose to the last dose of study drug, lasting 24 months)
Once everything is ready, you will either receive the treatment pills or dummy pills (you will not be able to tell which is which, they would both look the same).
The study drug is taken once a week for the first three weeks of every month.
The initial three visits will be in person 2 weeks apart to ensure participant safety, followed by monthly visits thereafter (24 months). If things are fine some of these visits will be converted to telephone calls.
During each study visit, we will go through clinical assessment, compliance on the treatment and check for any side effects, as well as laboratory tests for safety and measures of efficacy. There is an MRI scan at baseline (time 0), year 1 and year 2. There is also an LP at these three visits for the oligoclonal band test (antibodies) to see if individuals on Ixazomib loose their antibodies over time.
If you are happy to have further discussion about your participation in SIZOMUS: Please feel free to contact me
Dr Mohammad Aboulwafa (Dr Wafa)
Clinical Research Fellow for the SIZOMUS trial
11D department of Royal London Hospital: 02035540637 / 02035540638
Disclaimer: Please note that the opinions expressed here are those of the author Dr Wafa and 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.