Our £60,000 rituximab fund is still available to be put towards a full-scale clinical trial | 12 September 2015

The ME Association Board of Trustees are to keep open the £60,000 fund they have ring-fenced since 2013 to put towards a clinical trial of rituximab, they agreed this week.

In view of the uncertainty surrounding the starting date of the proposed clinical trial that will involve a group from University College London (UCL), they have decided to extend the closing date for applications for this funding from their dedicated Ramsay Research Fund from July 2015 to July 2016.

Click on the following link to read what they had to say about this fund in July 2013: www.meassociation.org.uk/2013/07/what-is-the-me-association-doing-about-rituximab-8-july-2013/


IN A STATEMENT ISSUED TODAY, THE BOARD SAID:


As before, any application for a grant from the MEA RRF must comply with the normal application procedures that we operate for consideration and approval of all research grant applications.

“This includes the applicant providing details of the protocol, location, staff involved, ethical approval, costings, etc.

“The completed application form will then be subjected to the normal peer-review process that all research funding organisations should follow.”

The statement continues that ME Trustees are very happy to receive applications:

1 From the UCL group, if they require any further funding for the trial that is currently being considered, and for which funding is currently being raised by Invest in ME.

2 From any other reputable clinical trials group – preferably one that is based here in the UK – that already has experience in using rituximab and is interested in conducting a clinical trial involving ME/CFS. We would consider an overseas application, especially if this is a mulitcentre trial that involves the UK.

3 To help co-fund a phase-3 randomised controlled trial. This is because we believe that independent confirmation of the efficacy and safety of rituximab in ME/CFS, along with identification of which clinical and/or pathological characteristics of people with ME/CFS make them more likely or less likely to respond to the drug, is going be essential if this expensive drug is going to be approved and recommended for use in ME/CFS by NICE here in the UK.

“We also believe that serious consideration must now be given towards setting up a phase-3 clinical trial here in the UK before we have the results from the phase-3 clinical trial that is now taking place in Norway. The Norwegian trial is planned to finish in 2017 but it may not be till 2018 that the results are available and published.

“To wait until 2018 before setting this process in motion here in the UK would mean that it would then be 2020 or 2021 before we had the necessary information from a UK trial phase 3 trial that might then persuade the NHS funders to make this drug available here in the UK for at least a sub-group of people with ME/CFS (assuming that the results confirmed safety and efficacy). That is a very long time to wait.”

MEA medical adviser, Dr Charles Shepherd, has already raised the issue of a phase-3 clinical trial here in the UK with the Board of the UK CFS/ME Research Collaborative.

Dr Oystein Fluge from Norway will be speaking about the phase-3 trial during the clinical trials session at next month’s 2015 Research Collaborative conference in Newcastle.

Dr Shepherd would be very happy to talk to any research group who wish to make a preliminary enquiry regarding this MEA RRF funding offer.


REPORT ON THE PRESENTATION ABOUT THE NORWEGIAN CLINICAL TRIALS GIVEN BY PROFESSOR OLAV MELLA AT THIS YEAR’S INVEST IN ME CONFERENCE


Professor Olav Mella, Haukeland University Hospital, Bergen, Norway: Multi-centre clinical trial of rituximab

This was the most impressive and informative presentation of the day.

Olav Mella started off by summarising some key points in the history of their work involving rituximab as a possible form of treatment ME/CFS – starting off with the observation that after treating a small number patients with Hodgkin’s Lymphoma, who also had ME/CFS, there was a marked improvement in their ME/CFS symptoms.
Reference: www.ncbi.nlm.nih.gov/pubmed/19566965

This was followed up by a double-blind placebo-controlled trial involving 30 people with ME/CFS – which again indicated that this drug could be a safe and effective form of treatment for at least a sub-group of people with ME/CFS. These results were published in 2011.
Reference: www.ncbi.nlm.nih.gov/pubmed/22039471

The was followed up by what is called a phase-2 study involving 29 patients. This trial involved both induction and maintenance treatment with rituximab for up to 15 months, with 36 months of observation. Results from this study are now published and confirm that Rituximab can produce a clinical response in 2/3 of people with ME/CFS with about half of those treated having a sustained response at the end of the 36 month observation period.

Based on this work, there is a now a much larger randomised, double-blind, placebo- (ie saline and albumin) controlled multi centre trial in progress in Norway involving both induction and maintenance treatment. The trial started recruitment in five centres (four university hospitals and a community hospital) in September 2014 with 120 out of a projected total of 152 patients being recruited by May 2015.

These patients meet Canadian criteria for ME/CFS and have an illness duration of two to 15 years.

Rituximab (500mg/m2) will be given on days 0 and 15, and then 500mg at 3, 6, 9 and 15 months. Patients will monitor themselves and an SF36 assessment of overall health status will be done every 3 months. Electronic activity, using a wrist band, will be measured at zero and 18 months. Blood samples will be regularly taken for biobank freezing. The primary end point is level of fatigue at 24 months. The secondary end point will be changes in quality of life, and any effects of toxicity.

Based on the assumption that there may be a diminished ability of blood flow regulation in ME/CFS (based on research that has already been carried out in Dundee), and that this could play a role in some ME/CFS symptoms, a sub-study to investigate endothelial dysfunction in the large arteries (the endothelium forms part of the blood vessel wall) before and after treatment will be carried out. People with gastrointestinal/bowel symptoms will also form another sub-study group. Changes in aerobic threshold will also be measured.

The main study will be unblinded for analysis when the last recruited patient has been observed for 24 months, which should be in the early autumn of 2017. So we should have news of the results of this trial in 2018.
Reference: clinicaltrials.gov/ct2/show/NCT02229942

Olav Mella also reported on another phase-2 study which is assessing the use of pulse infusions (i.e 6 infusions every 4 weeks) of an immune system modulating drug called cyclophosphamide. This will involve 40 people with ME/CFS split into three groups – those who have not been involved in any previous trials; those who have been treated with rituximab but not responded; those who have responded to rituximab but symptoms recurred. More information on this trial can be found on the MEA website:
www.meassociation.org.uk/2015/02/second-anti-cancer-drug-now-being-investigated-in-norway-for-treatment-of-mecfs-10-february-2015/

MEA statement on results of the phase-2 clinical trial from Norway:
www.meassociation.org.uk/2015/07/comments-


THE USE OF RITUXIMAB IN OTHER CONDITIONS


Finally, it is encouraging to note that clinical trials involving rituximab in a number of conditions that have clinical or pathological overlaps with ME/CFS have taken place, or are now taking place. These include its use in:

1 Lupus/SLE

www.lupusuk.org.uk/want-to-know-more/from-the-national-magazine/14-latest-news-archive/106-biologic-breakthrough

This summary is well worth reading and covers the possible reasons why some people with lupus respond to rituximab whereas others do not.

2 Myasthenia gravis

www.ninds.nih.gov/disorders/clinical_trials/NCT02110706.htm

3 Polymyositis and myositis

www.ncbi.nlm.nih.gov/pubmed/23124935

4 Primary biliary cirrhosis

https://clinicaltrials.gov/ct2/show/NCT02376335

5 Sjögren’s syndrome

www.ncbi.nlm.nih.gov/pubmed/24727841

Safety and efficacy in autoimmune disease: a general review

www.arthritis-research.com/content/13/3/R75

DR CHARLES SHEPHERD
Hon Medical Adviser, MEA

12 September, 2015