Status of Rituximab-ME/CFS Studies

This is an attempt to summarise the status of current and prospective clinical trials of Rituximab as a treatment for ME/CFS:

Fluge & Mella - phase II - Under way
- This open-label study is testing alternative dosage protocols.

Fluge & Mella - phase III - Not yet underway
- This is to be a large sample, double-blinded placebo-controlled study;
- They have substantial funding from the Norwegian government, but are currently trying to raise additional funding;
- This study is likely to utilize the findings from their current study (see above), and so isnt likely to commence until they are at least 6-9 months into that current study;
- Publication is probably 3 years away.

Spanish researchers - ?? - Under way ??

Dr Derek Enlander has stated a desire to conduct a replication study in conjunction with Dr David Bell, but they would have to raise the funding first (ie they'd be trying to replicate the findings of Fluge and Mella's 2011 publication).

Dr Andy Kogelnik is currently treating some ME/CFS patients with Rituximab (off-label), and is said to be expecting to have a formal clinical trial running by the end of 2012. He's proposing to treat patients with the combination of Rituximab and an antiviral. He's been trying to get this trial going since 2010.

Dr Klimas might also be trying to arrange a study.


Any corrections and additional info would be welcomed



[THERE IS AN UPDATE VERSION OF THIS SUMMARY BELOW (thread submission #8)]

Thanks for the list Persimmon. IT does indeed seem like Rituxan is beneficial for a subset of patients. I'd really like to see us push for getting more funding for these trials. Money of course is what we need. We can request state and federal funding, perhaps put together a patient drive, and also maybe, if organized effectively, would get the media's attention.

There is also this study at Haukeland Hospital in Norway, showing as currently recruiting participants:
http://clinicaltrials.gov/ct2/show/NCT01156922?term=NCT01156922&rank=1

It is for severely affected patients, expected number of participants: 10. Five are to be treated with plasma exchange 2-3 weeks before Rituximab infusions. Estimated completion date December 2013.

Can someone please elaborate on what subset of patients with CFS would most likely benefit from receiving Rituximab.

None. But patients with ME or MS will.

I think the study authors said that those who have had the disease the shortest period would have the best chance (which is what we'd expect). Other than that, I haven't heard anything.

UPDATED VERSION

This is an attempt to summarise the status of current and prospective clinical trials of Rituximab as a treatment for ME/CFS:

Fluge & Mella - phase II - Under way
- An open-label study
- Aim: to test the impact of adding maintenance treatments of Rituximab (at 3, 6, 10 & 15 months) to their existing protocol
- Follow-up period: 36months
- n=30 (sample size)
- Expected completion of data collection December 2013 (so publication would be unlikely before mid 2014)
http://clinicaltrials.gov/ct2/show/NCT01156909?term=kts-1-2008&rank=2

Fluge & Mella - phase II - Still recruiting (but might nevertheless have commenced the trial)
- An open-label study
- This study differs from their other current Phase II trial in two key ways:
(i) The cohort for this trial is to consist of (only) severely ill ME/CFS patients
(ii) Up to half of the patients in this trial are to receive plasma exchange as well as Rituximab (see notes below on plasma exchange therapy**)
- n=10
- Follow-up period: 36mths
http://clinicaltrials.gov/ct2/show/NCT01156922?term=NCT01156922&rank=1

Fluge & Mella - phase III - Not yet underway
- This is to be a large sample, double-blinded placebo-controlled study;
- It is to be a multi-center study, conducted at several Norwegian university clinics;
- They have substantial funding from the Norwegian government, but are currently trying to raise additional funding;
- This study will utilize the findings from their current (n=30) study. It's final design will be influenced by those findings, and so it can't commence until they have collected at least preliminary data from that current study. It's been reported in Norway that the study may commence in summer (ie northern hemisphere summer);
- Publication is presumably more than 3 years away.

Spanish researchers - ?? - Under way ??

Dr Derek Enlander has stated a desire to conduct a replication study in conjunction with Dr David Bell, but they would have to raise the funding first (ie they'd be trying to replicate the findings of Fluge and Mella's 2011 publication).

Dr Andy Kogelnik is currently treating some ME/CFS patients with Rituximab (off-label), and is said to be expecting to have a formal clinical trial running by the end of 2012. He's proposing to treat patients with the combination of Rituximab and an antiviral. He's been trying to get this trial going since 2010.
[In his proposed trial, he'd like to use a new antiviral, valomaciclovir, but has been struggling to get permission to administer it for periods in excess of one month. If he can't use this, he'd use Valcyte instead.]

Dr Klimas might also be trying to arrange a study.

[** Plasma exchange therapy
This is used to treat various immune system disorders, including a number of autoimmune diseases. It involves removing whole blood from a patient; separating the blood cells from plasma and discarding the plasma. The blood cells are returned to the patient, along with replacement donor plasma (or a combination of albumin and saline in lieu of donor plasma).
The treatments rational is that it is a way of removing large numbers of harmful antibodies (including autoantibodies) from a patients whole blood.
Plasma exchange therapy is often offered in conjunction with immuno-suppression therapy (eg Rituximab). The combined therapy aims to rapidly remove harmful antibodies from the patients blood, and then to block the production of new, harmful antibodies.
The patients receiving this therapy in one of Fluge and Mellas clinical trial will have up to 5 plasma exchange treatments, administered over a 1-2 week period, with that period being 2-3 weeks in advance of the commencement of Rituximab treatment.]


Any corrections and additional info would be welcomed

Cort posted on Corinne's visits to Dr. Peterson and on Day 4 one of the questions he answered was about Rituximab. Basically he said that he believes that there will be a subset of patients with CFS with an autoimmune component who might benefit from Rituximab. He also mentioned about the possibility of serious side effects and would want Roche to do a multi-centered drug trial.

The study says the criteria was: "a diagnosis of CFS by a neurologist, according to the Fukuda 1994 criteria [5], age 1865 years, and written informed consent. Exclusion criteria were: fatigue not fulfilling CFS criteria, previous malignant disease (except basal cell carcinoma and cervical dysplasia), previous long-term immunosuppressive treatment, previous Rituximab treatment, endogenous depression, lack of ability to adhere to protocol, or evidence of on-going infection."

You can see more details in the study itself: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026358

"- Publication is probably 3 years away."

Excuse me?!??! They said if the next trial went well, Rituximab would be out a year later, now its sudenly THREE??? They better not mess with me like this, I've taken a year in consideration now. :Retro mad:

The cohort is further described in a Research1st digest entitled "Rituximab Trial Shows Promise:"

Hi Tia,
I could be wrong! I don't have any inside knowledge - this thread merely started as an amateur's attempt to put together pieces of publicly disclosed info.

It's certainly frustrating that a topic so promising/important to so many people is not treated with greater priority by the medical research community. How can it be that nobody else has started a trial, nor seem close to doing so... I'm unsure whether Fluge and Mella have yet got the funding to hire a molecular biologist to trawl through the samples they already have in storage (which is a critically important thing to do).

As for the timing of their Phase III trial (the big one), they've said in interviews that they haven't decided on the details of this study's design. These details will depend on results from their current trials. Presumably the maintenance treatments are the key thing they're looking at, but possibly the follow-up period is up in the air as well. However these details work out, it's hard to imagine they'd have started this study in less than a few months time; it's hard to imagine it would run less than 2 years; and after that they'll be a delay before publication. If they start in the second half of this year and do 36 months of follow-up (as in their current trials) - both plausible assumptions - then final publication wouldn't be expected until at least early 2016!

Hopefully they'll publish results from this study before then, even if just preliminary findings. Hopefully there won't be a big delay in getting this study started - they still need to raise funds; then they have to select several hundred study subjects, and to get several separate university hospitals organised to participate.

It's pretty clear that Fluge and Mella want to do solid research - they won't compromise the design of their study; they won't be hurried. (They've already been working on this for 7 or 8 years.)

Q&A on the Norwegian trials:

http://www.meassociation.org.uk/?p=8459

Rituxan

I'm starting treatment in a month. Does anyone else know of anyone here who also is getting it before trials? I have a pretty severe case with the pain levels and fatigue.

thanks for making this thread Persimmon!

2014..*sniffles* Wow..

Wow, I didn't know they'd been at it for that many years, but 4 years..wow, I can't wait that long.

MS Trust were reporting on trials involving Rituximab, but have said last year that they have been terminated in favour of a new drug similar to Rituximab but in development, named: ocrelizumab.

I am obviously interested in this development, not least to learn if this new drug will overcome the side effects present in Rituximab; and whether it will affect the Norwegian trial in any way. If anyone can find out, would they post it here or let me know?

I'll have a dig around too of course and might even drop the Norwegian's a line at some point.

MS Trust information: November 2011: http://www.mstrust.org.uk/research/drugsindevelopment/rituximab.jsp

Ocrelizumab: http://www.mstrust.org.uk/research/drugsindevelopment/ocrelizumab.jsp

Just to clarify. I am not saying the ME trial will go the way of the MS one i.e. be terminated. I am just interested to learn a bit more about a possible new drug that will do the same at Rituximab but potentially might have less dangerous side effects.

Original postings: http://www.mecfsforums.com/index.php/topic,11477.msg132387.html#msg132387