New Rituximab ME/CFS open-label phase II study with rituximab maintenance treatment

[charles shepherd]

@charles shepherd and @Sasha I think I must be misunderstanding but does the proposed rituxamb study by invest in M.E at UCL not fit the bill of a phase 3 trial here in in the UK?[/QUOTE]

My understanding is that no definite decisions have yet been made on the protocol for this UK trial, the location, and when the trial will start

Others may be able to provide more information here

 

[charles shepherd]

So roughly how many phase three trials are we talking of here and do you mean they would have to be done in the UK ? If so we'll be waiting for decades......

I think the conversation I had with Bob earlier answers your question:

Bob said:
I guess it's like proverbially knocking the authorities on the head with a successful research trial. With one study, they can uhm and ah, with two studies they might start to take it seriously, and with three studies they might finally take some action. Not that it should be like that, of course.
Bob - That's a very good way of summing up how things work here in the UK!

But I think we may need more than 3 good studies given the cost of this drug…...

 

[charles shepherd]

What do you think will happen if the Haukeland and UCL trials are successful in terms of efficacy, but no specific clinical characteristics/patterns are discovered that lets us identify who are most likely to respond? Lets say that by 2020 still nothing is discovered. Does this mean patients in most countries (who require what you mention) will be left in treatment limbo?

If that situation occurs it clearly makes it more difficult……

But, as I keep saying, positive results from a phase 3 trial in Norway, and some positive results from a smaller UK trial, are unlikely to be enough to bring this drug to market for ME/CFS here in the UK. The UK authorities will want sound consistent evidence on both efficacy and safety from a number of independent trials.

Which is why, IMHO, we need to start talking about a large possibly multi centre phase 3 clinical trial here in the UK….

 

[Snow Leopard]

If that situation occurs it clearly makes it more difficult……

Sign. Lives will be lost due to the dithering of the state.

Still, I am very thankful for your efforts and I hope you are successful in promoting another UK trial!

 

[charles shepherd]

Fairly comprehensive guide from Wiki to the clinical trial hurdles (1-3) that a drug has to go through before it finally gets approval:

https://en.wikipedia.org/wiki/Phases_of_clinical_research

 

[Scarecrow]

Which is why, IMHO, we need to start talking about a large possibly multi centre phase 3 clinical trial here in the UK….

For those of us in the UK, what do you think we can do as individuals (or groups) to make this happen?

 

[Sasha]

@charles shepherd and @Sasha I think I must be misunderstanding but does the proposed rituxamb study by invest in M.E at UCL not fit the bill of a phase 3 trial here in in the UK?

We don't have details of the trial yet, because the UCL researchers are doing pre-trial work on B-cells to try to pre-identify likely responders.

But I'm not sure the £400k or so that IiME have raised so far would yield a big enough trial on its own to convince NICE with its results (and I don't think that was the original aim, either) - I think the idea was to inform the science and to be taken as part of an international evidence-effort.

I'm no expert, though.

 

[Sasha]

For those of us in the UK, what do you think we can do as individuals (or groups) to make this happen?

Excellent question - we need to be all joining together and getting that going, if that's what we need - or whatever makes sense in terms of drugs with similar action such as cyclophosphamide.

 

[acer2000]

People with ME/CFS who have a clinical and/or immunological signature who are more likely to respond to a particular form of treatment.

As we learn more about the use of this drug, it may turn out that there are clinical characteristics - such as length of illness, type of onset - viral/non viral, degree of severity etc - that are linked to response rates

At there same time there may be immunological markers involving various parts of the immune system orchestra - cytokines, B cells etc - that help to predict response, or a non response

Has there been any investigations into what predicts response from Rituxan? I keep seeing that they get a response, but I'm curious if there are markers that have been reported. Also, has there been any investigation into what supposed "autoantibodies" are being knocked out? Or is there another proposed mechanism?

 

[Snow Leopard]

By the way, this is the (PLOS One) Academic editor of the above study.
https://www.tilburguniversity.edu/webwijs/show/c.m.vdrfeltz.htm
https://www.researchgate.net/profile/Christina_Feltz-Cornelis

Yes, a psychiatrist. The bias persists...

 

[Daisymay]

We have a meeting of the Board of the UK Research Collaborative next Tuesday at the MRC in London - so I will certainly raise this at the meeting

As noted in the MEA statement, there will be a presentation on Rituximab from Dr Mella at the Research Collaborative conference in October in Newcastle during our Clinical Trials session

So yes, I fully agree that we need to get people in high places looking at the possibility of setting up a phase 3 trial here in the UK sooner rather than later…

Great.

We also desperately need these "people in high places" to urgently and publicly, endorse the IOM/P2P statements that ME is a serious multi-system physical disease and to take steps to ensure the Royal Colleges etc take swift steps to make sure their members diagnose and treat patients accordingly.

There is no longer ANY excuse, these "people in high places" need to act and act now, it is scientifically and morally inexcusable for doctor to do otherwise.

 

[halcyon]

I think we need to study cohorts of strictly defined ME patients so that we can first show whether this drug reliably works in, say, cohorts of CCC/ICC ME patients in different countries

I've wondered about this. Aren't autoimmune diseases more common in those of Scandinavian descent?

 

[Scarecrow]

I've wondered about this. Aren't autoimmune diseases more common in those of Scandinavian descent?

Damn! Rules me out.

But congratulations if you're from Orkney or Minnesota.

 

[alex3619]

@Kati, that is why, for ME and CFS at least, Rituximab is so important. One by one they are losing their diseases ... fibro and IBS have had breakthroughs too.

 

[Kati]

@Kati, that is why, for ME and CFS at least, Rituximab is so important. One by one they are losing their diseases ... fibro and IBS have had breakthroughs too.

Yes, all agreed. But we should be on the look out for FM.

 

[Lynne B]

@alex3619, Sorry, everyone, don't want to hijack this thread, but do want to be reminded of the breakthroughs for fibro and IBS. Alex, can you help please?

 

[alex3619]

@Lynne B, these include possible diagnostic tests (the fibro one went commercial some time ago, a provoked immune test, but I have read nothing since then; the recent IBS test is for a subgroup and I forget the details), pathophysiology (I forget the ones for IBS, but fibro is often linked to small fiber polyneuropathy and small blood vessel regulation), and a bunch of others. I do not follow either IBS or fibro closely though. Someone else might be able to comment better than me.

I do wonder if fibro might not also respond to Rituximab.

Often these breakthroughs fail to be replicated or have other issues. Yet they keep coming.

 

[SOC]

SOC, it would be great if it were that simple, but I doubt it is...one of the patients in this study apparently developed ME after being infected with Borrelia, and they were one of the ones who got no benefit from the Ritux...however, this patient was also involved in one of the earlier Ritux studies, and in that one they did seem to respond! Since several people have talked about Chronic Lyme being partly an immunological disease, I don't think it would be too surprising if Rituximab had some effect on these patients.

I DID say I wasn't suggesting that was the specific reason. I was using it as an example of the type of thing that could be happening.

For example (not saying I think this IS the case, just pointing out how it COULD happen)

I also said,

I'm sure the real situation is a great deal more complex, but the point is that the 67%/33% pattern we're seeing could simply be an indicator of subsets (or distinct conditions).

 

[Xhale19991]

So I don't have the time to go through all of this right now.

Can someone just let me know, is this as good as it sounds? I usually read these things expecting to be dissapointed but this seems like it may actually be big news.

 

[barbc56]

Barb56, if they don't take Maes seriously, why do they refer to his recent findings in their paper? Gottfries is the one that found HSP60 epitopes that looked like Chlamydial ones in people with ME.

Now I'm wondering if it's a different Maes? I need to look this up. Maybe go back and edit my original comment as I would hate to disparage someone credible mistaking them for someone else. Facepalm!

Barb