Rituximab study in norway. An application to The Research Council of Norway

[deleder2k]

I really don't know much about it. I think they have conducted a study on the most severely ill, but I do not know the results. From my understanding, they respond less favorably, in general. I am sorry that I do not know more. I will try to ask at Haukeland. The second phase open study will be published in a few months, and hopefully they'll reflect on the topic.

 

[Adele]

Does anyone have any thoughts about whether it is probable that some sort of results will "leak" out of this study before it is final in 2017? I know that neither the participating medical staff nor the participants will know who got the drug and who got the placebo, but if several of the 150, lets say around 50 of them, start to improve in about six months time, that would of course be very interesting. And does anyone know if there were "leaks" from the phase II study before it was officially released? Did it all come as a major surprise to the ME-community when the results were published in October 2011, or was there a "bird singing some tunes" before that? I didn't really follow any of this myself at that time as I didn't get sick until after that.

Another question is about the role of the ethical committee which follows the trial, which will know who got what. I have been told that if the preliminary results are very good for the drug compared to the placebo, it will at some level of effect be seen as unethical to continue the study without giving the actual drug to all the participants. The study might in such a case be stopped and the drug will instead be given to all the participants. Does anyone have a clue about where a "limit" for such an intervention might be?

 

[Bob]

Does anyone have any thoughts about whether it is probable that some sort of results will "leak" out of this study before it is final in 2017? I know that neither the participating medical staff nor the participants will know who got the drug and who got the placebo, but if several of the 150, lets say around 50 of them, start to improve in about six months time, that would of course be very interesting. And does anyone know if there were "leaks" from the phase II study before it was officially released? Did it all come as a major surprise to the ME-community when the results were published in October 2011, or was there a "bird singing some tunes" before that? I didn't really follow any of this myself at that time as I didn't get sick until after that.

Some participants would probably make it known if they've experienced a drastic improvement. And the researchers might even indicate whether they're seeing a similar level/rate of improvement as the previous trial phases. Apart from that, I think the previous two phases of the trial might give us a good clue about what to expect. I can never work out exactly what the outcomes of the previous trials were. (Either I keep forgetting my interpretation of the results, or I never managed to get a clear picture.) But, from what I can work out, there do seem to be a number of remarkable responses to Rituximab, and there seems to be a decent response rate.

 

[Snow Leopard]

Does anyone have any thoughts about whether it is probable that some sort of results will "leak" out of this study before it is final in 2017?

Only if they release the results early. I don't know the details of the plan on independent review of the results/early release, but if so, I dare say it will be a play it by ear sort of thing by those who review the results. So no real guarantees of when the results will be published at this stage.

Yes, some participants may be vocal about their recovery, but they will be in the minority, and we still won't know whether the recovery was spontaneous or not until the results are released so..

 

[ukxmrv]

The other possibility is if one of the researchers attends a conference and lets slip about the results. I remember at the London IiME conferences there have been disclosures about research projects and the CD they produce has been held up because of an embargo on what someone said.

I can't see a list of the participants for the next iIME conference yet though (in 2015)

 

[Bob]

The other possibility is if one of the researchers attends a conference and lets slip about the results. I remember at the London IiME conferences there have been disclosures about research projects and the CD they produce has been held up because of an embargo on what someone said.

The lastest trial is blinded, so the researchers won't know any results until they unblind. I've no idea when they intend to get to that stage.

 

[Adele]

The other possibility is if one of the researchers attends a conference and lets slip about the results

That could of course be as soon as the researchers have got any material themselves. In this lecture (unfortunately in norwegian)

, Mella reveals some at that time unpublished findings from the follow-up studies after the phase II trial. But as the phase III study is double blinded I guess they will not have anything to tell before the study "unblinds" 24 months after the last participant gets the first infusion. And that will probably be in about 2,5 years from now.

 

[Bob]

That could of course be as soon as the researchers have got any material themselves. In this lecture (unfortunately in norwegian), Mella reveals some at that time unpublished findings from the follow-up studies after the phase II trial. But as the phase III study is double blinded I guess they will not have anything to tell before the study "unblinds" 24 months after the last participant gets the first infusion. And that will probably be in about 2,5 years from now.

They might perhaps get a feel for whether there is a similar response rate, before unblinding.

 

[Adele]

Yes, lets absolutely hope so! 2,5 years is waaaay to long a wait for something so fundamentally important to many of us! And that comes from me, who am a total newbie in this "game" compared to many here. Most of you will have been waiting for such results longer than I even want to think of. All my deepest sympathy to everyone who has been ill for very long.

 

[NK17]

@Adele thank you for the interesting discussion. As you well say many of us and many PWME around the world who are not on PR have been living with this Beast of a disease for many years and the wait for a possible DMT Disease Modifying Treatment seems, at times, like a torture.
Still I think that for the greater goodness we should try to be wise and not force to extrapolate too much from single anecdotal responses, or lack of thereof, from participants and should not leak out from Norway any potentially important information, that might jeopardize the whole phase III clinical trial.

I'm absolutely certain that Dr. Mella and Dr. Fluge with the rest of their collaborators have only and solely the best interest which is helping patient.

I'd like also to state that I've been thinking and looking forward to be treated with Rituxan here in the US since 2011. In a way I consider myself a patient/stakeholder .

My hope and greatest wish is of course that this phase III trial will pan out and bring us out of the dark ages of ME medicine and I think that these Norwegian doctors are seriously going to lead the way .

In the meantime let's try to hang in here (our failing bodies) a while longer!

 

[Adele]

I totally agree with you NK17 in that the last thing we want to do is anything that could be unhelpful to the study. But on the other hand I don't really see how we can possibly do that by thinking out loud or speculating around it. If one was to worry about an "added placebo effect" if speculations reach the participants, that would be the same in both the drug and the placebo group, which would then not make any difference. But there may of course be aspects of something that I do not see…?

And by the way, when it comes to placebo-effect, I guess that may already have been stronger for the previous trial than for this one. Those who went into that trial did so knowing that all three pilot-patients had had a remarkable effect. This time they know that the previous patients have had more mixed results (yes - I am looking for all positive hints that could ever be found here… )

Anyway I would say you are definitely a stakeholder for Rituxan in the US NK17 On my hand, I don't find it likely that I will wait for three years before trying the treatment, even if that means I will have to go abroad, probably to the US, and pay for it myself. For a while longer I am working hard on all kinds of alternative treatments, psychological angles and adjustments of life. These are things that many of you have probably been through a long time ago. And to some degree it works, things are improving very slowly. But if in a year or so I am still not able to go back to at least some reduced work, I think I will just have to try it. And if it works then that is amazing, if it doesn't I will at least know I tried.

 

[MEMum]

The other possibility is if one of the researchers attends a conference and lets slip about the results. I remember at the London IiME conferences there have been disclosures about research projects and the CD they produce has been held up because of an embargo on what someone said.

I can't see a list of the participants for the next iIME conference yet though (in 2015)

I think it would be pretty likely that F&M will attend the research collaborative meeting the day before the main IiME, as they did this year. I guess it's unlikely they would be able to share re the new trial, but maybe we could ask them re progress on the initial/pilot studies, via the Chair or the organisers.

I thought a couple of US researchers were starting Rx trials. ? Dan Peterson looking at antivirals and Rx. Anyone know what's happening re these?

Does anyone know the effect of Rx on fertility at the doses given for ME. I got the impression from my daughters consultant that he would not be keen for a 20 year-old to have Rx, but maybe he is looking at doses used for cancer treatment which may well be higher/more frequent.

 

[Bob]

I think it would be pretty likely that F&M will attend the research collaborative meeting the day before the main IiME, as they did this year. I guess it's unlikely they would be able to share re the new trial, but maybe we could ask them re progress on the initial/pilot studies, via the Chair or the organisers.

FYI, information on the Norwegian phase i and phase ii trials is already available on this forum.
I'm not sure exactly where that info is, and i always find it difficult to interpret, but it is available.

 

[deleder2k]

FYI, information on the Norwegian phase i and phase ii trials is already available on this forum.
I'm not sure exactly where that info is, and i always find it difficult to interpret, but it is available.

There are some information if one looks at my first post in this thread. Phase 2 open study is probably being sent in for publishing before christmas. Results are mainly the same as the double blind study. To my knowledge 6 out of 9 patients got significantly better in the open study.

 

[Snow Leopard]

They might perhaps get a feel for whether there is a similar response rate, before unblinding.

They won't have a feel for it, that is the point of double-blinding.

If they decide halfway through to do a review, then an additional group of people will be recruited to make that decision (based on some sort of specific criteria).

 

[Adele]

They won't have a feel for it, that is the point of double-blinding.

Well, if it shows up that around 50 people (+ some for the placebo-part) start making significant progress in about 6 months time or so, then I think one will get some sort of a feeling. That might show up as wrong in the end of course, but I don't think I would be the only one starting to feel (perhaps prematurely) happy and excited then But whether the researchers get to follow the group at all or receive any results for the group as a whole before the unblinding, that I don't know.

Does anyone know by the way? Whether the researchers get to follow the group as a whole along the way, or do they not receive any information at all until the finish line?

 

[Jonathan Edwards]

Well, if it shows up that around 50 people (+ some for the placebo-part) start making significant progress in about 6 months time or so, then I think one will get some sort of a feeling. That might show up as wrong in the end of course, but I don't think I would be the only one starting to feel (perhaps prematurely) happy and excited then But whether the researchers get to follow the group at all or receive any results for the group as a whole before the unblinding, that I don't know.

Does anyone know by the way? Whether the researchers get to follow the group as a whole along the way, or do they not receive any information at all until the finish line?

I have been involved in several multicentre trials over the years. Generally speaking you have no idea what is happening at other centres. Clinical assessment tends not to be done by the senior member of the local team and they mostly have no contact at all with other assessors. There are likely to be co-ordinators doing the rounds of centres, but since this not a commercial trial there may not be so much. Usually co-ordinators are able to make general comments about having heard of 'some good responses' but usually nobody really knows what to make of that until someone sits down with all the data.

 

[Bob]

They won't have a feel for it, that is the point of double-blinding.

The trial is blind but the physicians aren't so if, for example, a number of severely affected patients start responding after 3 months to the point where they can walk then that might give them a hint that the treatment is working as expected. I didn't say that they'd know the precise outcomes. I said they might get a 'feel' for the type of response they are getting. But Jonathan has explained how he expects the trial to be run, so it looks as if they will pretty much be ignorant in this case until they assess the data.