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UK recruitment success in rare disease trial offers hope to GVHD patients

Published: 31 December 2018

Our unified national network enables better recruitment for rare disease research.

Clinical need

Acute Graft Versus Host Disease (GVHD) is a rare condition. It is a possible complication that can occur in people who have received a bone marrow transplant as a treatment for a blood cancer such as leukaemia, lymphoma and myeloma. GVHD develops when white blood cells (immune system cells) in the donated bone marrow reject the body of the person who is receiving the transplant and begin to attack it. The condition is graded on a severity scale and can be fatal for those patients who experience severe GVHD, also known as Acute GVHD. The current treatment for severe GVHD is steroids however, on average, only 50 per cent of severe GVHD patients respond to the steroid treatment. Of the remaining 50 per cent, nine in every 10 people will die from the condition.

Cynata Therapeutics Ltd is a small Australian life science company which specialises in stem cell therapy. In 2017 Cynata brought a phase one study to the UK investigating the safety and efficacy of a new stem cell treatment for use in patients who have severe GVHD, and who have failed to respond to the steroid treatment. Dr Kilian Kelly, Vice President, summarises the aim of the study:

“There is a real clinical need for a new treatment for GVHD for those patients who do not respond to steroids. We have developed a new stem cell-based treatment which we hope will be able to reverse GVHD. The aim of the trial is firstly to check that the treatment is safe, and secondly to see if the treatment has a positive impact on the patient's condition and outcomes.”

Why choose the UK?

One of the key challenges for this trial is the unpredictability of recruitment due to the rarity of the patient population. With a target of recruiting 16 patients in total, Dr Kelly explains why Cynata decided to bring the study to the UK:

“When we started planning we didn’t have a particularly strong view on where we would conduct the study. We were keen to deliver it here in Australia, but we knew this would be difficult because the target patient population is so small, so we were quite open to extending the trial overseas as well.

“We picked the UK after speaking to a number of regulatory authorities in the UK, Europe and in other regions. We found that the Medicines and Healthcare Regulatory Agency (MHRA) was particularly helpful and very pragmatic in terms of what they required from us to be able approve the clinical trial in the UK. They provided very clear guidance about what we needed to do in terms of pre-clinical testing. This led us to the conclusion that we had a good chance of getting the trial approved in the UK quite quickly, compared to some other countries where the journey may not have been quite as smooth.

“We also looked at the recruitment potential and the quality of clinical research sites in a number of countries. Again, the UK ticked that box very well because there are a number of leading clinical research centres and investigators who indicated an interest in the study during our early feasibility assessments.”

Being a small life science company, Dr Kelly’s team decided to engage a global Clinical Research Organisation, with headquarters in the UK, to help deliver the trial. Joe Booth is a Regulatory Affairs Associate for The Clinical Trials Company (TCTC) - the CRO which managed the study in the UK and conducted the initial feasibility. Joe believes that Cynata made a wise choice when they decided to work in the UK:

“The UK is the ideal destination for this study. When you are dealing with a rare disease, the population density of a country is really important. In the UK we have many high density population cities such as London, Bristol, Leeds, Nottingham, Manchester - which made the recruitment target achievable. Australia’s population is a third of the UK’s and spread across a much larger area, making it harder to engage patients with rare diseases.”

NIHR impact

This fact became a reality when the study got underway in the UK and in Australia in March 2017. Originally Cynata had hoped to open four sites in each country, but it quickly became apparent that a competing study in Australia could seriously hinder recruitment efforts in the southern hemisphere. In response, Cynata decided to open just two sites in Australia and five sites in the UK. The combined UK recruitment target was to enrol ten patients, but the UK sites easily exceeded this target and successfully recruited 16 patients by May 2018. Dr Kelly continues:

“We expected the recruitment to be variable, due to the rarity of the patient group, so we are especially grateful for the efforts of the UK sites in helping us complete recruitment for this important study.”

As well as population density, Joe Booth feels that the UK has another advantage - the NIHR Study Support Service. He explains:

“I reach out to the NIHR Study Support Service when engaging with the National Health Service (NHS) on a new study, for a number of reasons. Firstly, we are a private CRO and sometimes find NHS sites can be quite protective, which us understandable, especially where there is no previous experience of working together. However, we find that if we work through the NIHR, the NHS sites are much more responsive to engaging with us in general, even down to responding to emails. And when we do need to motivate sites, the NIHR team have the relationship, and therefore the capability, to achieve results.

“Secondly, on this study, and on others as well, we have found that one of the main advantages of working with the NIHR is that we get realistic recruitment targets from the sites. In some cases we have found that if we approach sites directly there has in the past been a tendency for sites to perhaps overestimate what recruitment levels they can achieve. The feasibility element of the NIHR Study Support Service overcomes that by providing a sense check on targets by using local intelligence and by looking at what other studies might be competing for similar patients both nationally and locally. This is especially important when you are researching a rare disease. We want our sites to achieve their recruitment targets in the allotted time. We selected five sites in the UK, all five of those sites have recruited patients to the study. I would definitely say the support provided by the NIHR was a factor in the success of this study.”

Success certainly appears to be in the offing, in more ways than one. Results from the trial so far are extremely encouraging:

“We are extremely pleased with the results from the first phase.” says Dr Kelly. “We have not had any safety issues, which is obviously very important. Additionally, we have seen a very high rate of ‘response to treatment’, with some patients showing a complete response, which means that the GVHD has completely disappeared. This is a really positive outcome as all these patients have previously been unsuccessfully treated with steroids, which meant they really didn’t have a good outlook.”

With the final target of 16 patients achieved, Dr Kelly is keen to convey his experiences of working in the UK to other life science companies:

“We have now completed recruiting the second cohort of eight patients and are hoping for further positive safety and efficacy results when the final analysis is performed. Our message to other companies considering the UK as a destination for clinical research would be very positive. We have had a good experience both on the regulatory side, in terms of getting a trial approved, and also in terms of recruitment. We had heard views that recruitment in the UK could be slow, but that certainly wasn’t our experience and I think those views are outdated.”

Joe Booth agrees that there many benefits to be gained from working in the UK, compared to other countries:

“For example, finding the right sites was crucial for this study. We did our own feasibility, which we shared with the NIHR team, but the NIHR team were then able to cast the net much wider, to the whole NHS, and engage more sites. They got a very good response.

“The NIHR also provides access to tools such as study costing templates and standardised contracts hat you can take to any NHS site to help speed up study set up. They also have the ability to motivate sites and drive performance which cannot easily be achieved when working directly with a site. “In summary, my message to companies considering bringing a trial to the UK is that the main advantage is that you are accessing a unified system. It’s a really attractive selling point.”

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