ChariotMS is on a roll…

C

I’ve been neglecting my blogging duties, but I have an excuse, which is that I had the team and myself on ‘slogging’ duties to get ChariotMS underway:-)

ChariotMS is an ‘investigator-led’ trial, and that really means doing all related jobs yourself, from protocol writing to participant-information & consent sheets, case report forms, database, statistics, randomisation system, in short: everything. I say everything, but there are some significant exceptions such as randomisation, part of the lab tests, and – of course – the drug we’re going to test, which is made & shipped by Merck (and hopefully not held up at the new Brexit barrier…).

Anyway, a few weeks ago we had our meeting with the Westminster Research Ethics Committee, and bar a few minor issues, they were happy with our submission, as was the MHRA, so we’re on track to recruit our first participant on 4th of Jan 2021 !

A huge credit to the team, particularly our (relative) newbie and principal trial manager, Harpreet Mangat, digital editor and PPI member Christine Chapman, who is responsible (for example) for this, and David Lieberman, who not only helped writing the protocol and many of the ancillary documents, but with the myriad of discussions & meetings that go into such a project. The list of people having carried ChariotMS to this is stage is long; I will introduce them in due course so they all get the credit they truly deserve.

Whilst we will update here on the blog, and soon activate a dedicated ChariotMS website, the MS Society has kindly taken the lead on PR for now, closely watched by all who contributed no small amounts of cash and other support, including the MRC/NIHR-EME, the National US MS Society, Barts Charity and Merck KGaA (Thank you all!).

The MS Society will produce some flurry of activity about ChariotMS across platforms later this week, in the context of their STOP MS campaign and Christmas appeal (I trust you’ve also read yesterday’s post by MD explaining the lenghts & depths the MSS has gone to select the most promising add-on candidates for progressive MS; who knows ChariotMS might lead to a platform on which future add-ons could be layered) – please support them if you can, and remember ChariotMS currently includes only 2 years follow-up, so we need additional funding for an extension study to make it 4 years in total, and the initiative to gather momentum for this starts now. It be unforgivable if we wouldn’t follow-up the 200 pwMS enrolled in ChariotMS beyond 2 years. Though we are hopeful to detect the effect of treatment after 2 years, it might take a little longer than that to reach statistical significance; I’ll get back on this!

@KlausSchmierer

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19 comments

  • When would the drug actually be taken by those on the trial and how often would the participants be required to travel to st. Bart’s?

    I ask this because January does not appear to offer a safe picture for people with MS to both travel and engage in new immunosuppressive drugs.

    We are told people with MS whose edss is greater than 6, which would be everyone on your trial because they are in wheelchairs, are 6 times more likely I believe to die from covid. Many of these people including myself have only been out a handful of times since March

    We are now told that should the vaccines be effective that we would be looking at potentially next Winter before life reverts back to normality.

    Would it not be better to start the trial at the end of next year?

    • ProfK will reveal all, but as Merck has supplied the pill this can be taken at home. The number of visits have been reduced to be COVID-friendly and remember that Barts is open for delivery of immunosuppressive drugs. However you are correct that EDSS above 6 is a risk factor for worse COVID-19. There will be risk mitigation put in place. The trial has already been put on hold and setting up the infrastructurehas costs

    • Your concern is real, and we regularly review process to mitigate the risk. It will never be zero. And whilst the study has the all clear now, we expect a bumpy ride in terms of recruitment. Places under significant current COVID-19 stress, such as Scotland, will open later than others; it will be phased. However, investment has been made, and delaying the study would come at a huge cost, running the real risk that ChariotMS would not reach its targets. We have worked eight years to get here; we want participants to be as safe as possible; there would be a massive cost for pwAMS if we’d stall now.

  • Great news – there is no time to lose! Brilliant to see so many researchers, clinicians and patients working together. I share the concerns expressed about trial participants’ travel to St Barts (and other investigator sites) and wonder if bloods and other safety tests could be taken locally at GP surgeries/clinics and consultations/questionnaires/other visible tests performed online via Zoom or equivalent?

    Loved the film, Christine! Fast paced which reflects the speed at which we need to move!

  • Prof K,

    Thanks for your work on this project. The aim of the trial is to test whether: “Cladribine tablets halt deterioration in people with Advanced MS”.

    I thought Cladribine tablets were already used in RRMS, so is there any evidence that these tablets halt deterioration in these patients (given that many consider MS to be one disease and that progression is there from the start)? Or are these tablets different / being used differently in the patients with Advanced MS?

    • Good question highlighting the limited accuracy of these descriptors. With the term “advanced MS” we decided to cover anybody with an EDSS of 6.5 and above. Though sounding crude, this distinction is probably least presumptive in a pathophysiological sense. “Progressive” or “relapsing-remitting” MS imply specific underlying mechanisms, and this is where the debate about MS being 1, 2, or 3 diseases starts. Using a disabilty cut-off is non-committal with respect to the underlying mechanism. We do assume that inflammation continues to play a role in the vast majority of pwMS throughout their journey, based on pathology nearly 80%. If that is the case, and provided cladribine can address this inflammation, we hope to detect a measurable difference between active and placebo arms.

      • Let’s hope that is the case….i.e. starting clad early before EDSS 6.5! Teri does not seem to be working for me so beginning clad in 2021. I have been monitoring my lymphocytes since stopping the anti-CD20 and they are all over the place, with CD4s being extremely high.

  • Great work Prof K. Heres a thought if caldribine was effective against primary or secondary MS, then those taking caldribine for their RRMS, will not develop progressive MS or delay the inset significantly right? We both know this doesn’t happen. Otherwise it would be called a cure. But hey gets to have another indication for their drug and more revenues. Great job barts. Why waste money and resources to see if MS can be cured with antivirals.

    • You know what is really frustrating, individuals who talk sh#t yet hide behind “anonymous”. Grow some balls and put your name on these posts. Prof. K is doing amazing work. Read my recent posts, I used anti-cd20 followed by a DMT with antiviral aspects…….it did not work!!

      • Tom,

        I was wondering how your iteri study was working out. Sorry to hear that the answer seems to be not very well. Can you direct me to your post on this as i must have missed it. Hopefully cladribine serves you better

        Thanks

        • Despite my frustration with anonymous posts, I am a nice guy and committed to sharing my experiences and MS journey.

          Due to adverse reactions, I had to stop the anti-CD20 in Jan 2020. I wanted to wait for my cd20 b-cells to repopulate before hitting my immune system with another DMT sledgehammer. Knowing the potential relapse risk during b-cell repopulation and my apparent sensitivity to the sledgehammer DMTs, I decided to use a lower efficacy DMT with anti-viral aspects in the interim.

          Began monitoring my lymphocytes monthly. In July 2020, my cd19 b-cells remained depleted and I started teri. MRIs of brain/spine in August 2020 showed new lesions, which were not enhancing, so the anti-cd20 did not keep my MS at bay. In October 2020, cd19 b-cells began to populate (2/ul) and I started to relapse. November labs showed cd19 at 32/ul. Obviously, I have a highly active disease course and the immunologist said my response to these DMTs (and coming off the DMTs) seems to abnormal. CD4 and CD8 jumped well above upper limits during cd19/cd20 population.

          Before starting clad in 2021, I will test my EBV levels to see if there is any change from my pre-DMT tests. My experience with the iTeri theory only represents a sample size of 1, so this does not prove or disprove the hypothesis. I am just trying to slow this horrible disease down.

          • Thanks Tom. Sounds like a rollercoaster. In terms of moving from one sledgehammer to another, what is the theory is trying to avoid this? For instance, to go from anti CD20 to HSCT wouldnt that mean that you were just clearing what was left on the immune system i.e half the job was already done? I do hope it works out for you anyway. On the anonymous posts, I get the frustration when people are hurling abuse but that’s not true of all of them

    • ANONYMOUS: “We both know this doesn’t happen” I believe the jury is still out “in which proportion this doesn’t happen”; we simply don’t have the long term data as for some of the other highly effective DMTs. And they show that even the most effective will have a significant number progressing. Extending the license is really way off. All going well, ChariotMS will report at the end of 2024. Now, let’s assume the study is positive; what happens then? Unless the regulators move the goal posts, such a result would support undertaking a phase III ‘registration trial’, with likely at least 3 years follow-up, so we’re looking at 2030 for the readout. Not exactly a short term win!

  • Annonymous 7:18pm Nov. 19 – you asked “ In terms of moving from one sledgehammer to another, what is the theory in trying to avoid this?” Answer – Death, PML, and additional adverse reactions.

    Since Ocrevus landed me in intensive care, I would like to avoid this with another sledgehammer. Also, I see an immunologist and he said I clearly do not fit into the standard with respect to expected immunological responses to DMTs. They need to start incorporating individual genetic make ups into DMT safety and efficacy assessments.

    Since the drug companies and doctors cannot provide me with the necessary data, I am no longer willing to blindly follow their recommendations, which tend to be influenced by ties to big pharma and their egos! I know I need a big gun to control my disease, just not willing to die in the process.

    • I see….to explain, I was only asking as i have also recently started Ocrevus but my experience so far hasn’t been great. A long way from your own I have to say but I am considering whether I should be planning another route and took interest in your posts as they always seemed well thought through….I didn’t know whether I was missing something and that moving to say, lemtrada or hsct was unwise. Best of luck with mavenclad and thanks for the reply 👍

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