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Rare Disease Research Across the Network

Vital rare disease research is being undertaken by many Registered Clinical Trials Units (CTUs).

There are thousands of rare diseases that collectively affect millions of people in the UK. Because each condition itself is rare, it is challenging to do clinical trials to show whether new treatment approaches are safe and effective. Sadly, this means many rare diseases lack effective treatment with no research ongoing to give patients hope. Read more about the importance of research into rare diseases here.

Registered CTUs are helping to tackle these challenges by improving how rare disease research is designed and delivered. You can explore a few of these important and innovative trials below.

rEECur: Balancing clinical efficacy against toxicity

The rEECur trial is the first international, large-scale randomised controlled trial for recurrent and primary refractory Ewing sarcoma (RR ES). Given the rarity of this paediatric cancer (approx. 250 UK cases annually) and its poor prognosis, rEECur utilises a multi-arm, flexible design to maximise data from a limited patient pool.

Over the past decade, the trial has evaluated 6 different chemotherapy regimens, aiming to identify the optimal systemic treatment by balancing clinical efficacy against toxicity. Of the first 5 arms compared within the trial, high dose ifosfamide (IFOS) has been defined as the most effective regimen at prolonging survival, and is now offered to patients at first relapse as standard.

There are currently 2 arms open to recruitment; IFOS and IFOS combined with lenvatinib (IFOS-L). Lenvatinib belongs to a class of drugs which has shown promising activity in relapsed disease, with an acceptable toxicity profile. A new treatment, trabectedin plus irinotecan is being added into rEECur with the aim of opening in the UK in summer 2026.  The inclusion of trabectedin is underpinned by promising data which has demonstrated clinical benefit in ES. These drugs offer hope to patients who might not otherwise have access to potentially more effective and less toxic drug combinations, providing better quality of life. The Cancer Research Clinical Trials Unit (CRCTU) at the University of Birmingham provides the infrastructure and expertise needed to deliver rEECur including involvement in protocol development and design and regulatory navigation ensuring the trial is scientifically robust and ethically compliant. Delivery is supported through supply of drugs unavailable via local hospital supply, centralised data management, monitoring and safety reporting which ensures the integrity of the results and the wellbeing of participants. By managing these logistical and administrative requirements, the CRCTU ensures that trials are conducted to the highest standards.

Acknowledgements: Prof Martin McCabe (Chief Investigator), Cancer Research UK (funder)

CF-10: Identifying a better treatment for cystinosis

Cystinosis is a rare inherited recessive condition, with a frequency of 1 in 100,000-200,000 live births, that, if untreated, causes kidney failure and death. There are only about 2-3 new cases each year in the UK.  Standard treatment is cysteamine, which has unpleasant side effects and needs to be taken very frequently, so better treatments are needed. CF-10 is a cysteamine prodrug that was designed to eliminate the deleterious side effects of cysteamine, and does not need to be taken so frequently, and hence may be a superior treatment for cystinosis.

The CF-10 trial is the initial step in the evaluation of CF-10; it is a Phase 1 clinical trial, funded by the Medical Research Council, to estimate the best dose and safety of this potential new treatment. The trial is co-ordinated by the Cancer Research UK CTU in Birmingham, and is expected to open to patient recruitment next year.

MCDS-therapy: Improving treatment for children with skeletal dysplasia

This trial assessed whether carbamazepine (CBZ) presents a promising treatment for children with skeletal dysplasia. It was a designed as an efficient two-stage trial, first choosing a safe dose of CBZ and then assessing whether it led to improvements in growth and symptoms such as pain.

Funded by the EU’s Horizon programme and coordinated by Newcastle CTU, recruitment opened across multiple international sites. Conducting an international trial in an ultra-rare paediatric condition presents considerably challenges, but such a collaboration is necessary for extremely rare diseases. The CTU model provides the operational coordination, statistical expertise and governance oversight needed to deliver this type of complex global study.

Find out more here.

OPERA – Optimising Primary Therapy in Primary Billiary Cholangitis

This is an ongoing trial, funded by NIHR and coordinated by Newcastle CTU. It is enrolling participants with Primary Biliary Cholangitis (PBC), a rare autoimmune liver disease. Participants identified as being at high risk of not responding adequately to first-line treatment (ursodeoxycholic acid, UDCA) are randomised either to continue UDCA or to move directly to second-line therapy (obeticholic acid).

Because PBC is rare, feasibility is critical. OPERA employs advanced statistical analysis approaches that allowed the sample size required to be reduced by 30% without compromising scientific robustness. This is making the trial more feasible to complete.

Find out more here.

TreatWolfram: Evaluating a promising treatment for Wolfram syndrome

Wolfram syndrome is a rare, genetic life-limiting disease, causing diabetes and blindness in children, and death in mid-life from damage to brain cells and brain shrinkage. There is no cure, and no treatments to prevent or slow down the disease. Sodium Valproate was found to be a promising treatment in cell models of Wolfram syndrome, so the TreatWolfram trial was initiated to evaluate whether it was able to slow disease progression.

This was an international, placebo-controlled trial, co-ordinated by the Cancer Research UK CTU (Birmingham), and measured the effects on vision and neurological degeneration over 3 years. The trial recruited 63 patients from 6 sites in 4 countries; it has completed follow-up and is currently in analysis, with results expected soon.

Find out more here.

Looking ahead: Accelerating rare disease research

Recent funding from Lifearc has established the Centre for the Acceleration of Rare Disease Trials (ARDT) which brings together several CTUs with a strong track record in rare disease trials. ARDT will support the streamlining of design and delivery of trials in partnership with patients. We are confident that this will catalyse many more rare disease trials in the future, helping to improve outcomes of patients who currently lack treatment.

To find out more about the work of Registered CTUs, including ongoing rare disease research, follow the Network on LinkedIn and Bluesky.