DefINe

A randomised, double-blind, placebo-controlled trial examining the safety and efficacy of deferiprone in patients with neuroferritinopathy              

Research summary

Neuroferritinopathy is a disorder caused by a mutation (fault) in a gene which leads to iron gradually building up in the brain. The build-up of iron eventually leads to the death of brain cells (called neurons), and certain brain regions that help control movement are particularly affected.

There are no treatments known to reduce or slow the progression of neuroferritinopathy. Some treatments are available to help with the symptoms of neuroferritinopathy, but these may only be effective for a limited amount of time and have significant side effects.

Deferiprone is a medication that is used to remove excess iron from the body and is licensed for use in the UK for a condition called thalassaemia major. It has been shown in a related disorder that deferiprone is able to reduce brain iron and slow clinical progression, and we now want to test this in people with neuroferritinopathy. The purpose of the trial is to test whether deferiprone can reduce the iron build-up in the brain of people with neuroferritinopathy.

Participants in this trial will take tablets twice a day for 12 months. There is a 50% chance (much like flipping a coin) that the tablets will contain deferiprone. The other half of participants will receive a ‘dummy drug’ called a placebo. Neither the participant nor the trial doctor will know which treatment is being taken, although the trial doctor can find out if necessary.

The trial is being conducted in Cambridge, although participants may be recruited from elsewhere. Participants will need to attend four in-person visits in Cambridge over a 12-month period, as well as have monthly phone calls and regular blood tests between the in-person visits. A final phone visit will take place at 13 months.

To be eligible, participants must have a genetic diagnosis of neuroferritinopathy, be aged 16 or over, and fulfil additional eligibility criteria.

Main inclusion criteria

  • Be aged 16 years and over, of any sex and gender

  • Be willing and able to provide written informed consent 

  • Have a genetic diagnosis of neuroferritinopathy (mutations in FTL gene) 

  • Have symptomatic neuroferritinopathy 

  • Be able to undergo magnetic resonance imaging (MRI) brain imaging 

  • Agree to use contraception as outlined in the trial protocol

  • Be able (in the Investigator’s opinion) and willing to comply with all trial requirements 

Main exclusion criteria

  • Conditions or use of medicines known to contraindicate the use of deferiprone (e.g. history of agranulocytosis or recurrent episodes of neutropenia) or known hypersensitivity to deferiprone or any of its excipients. This includes human immunodeficiency virus (HIV) positive or other immunocompromised patients. 

  • Neutropenia (absolute neutrophil count [ANC] < 1.0 x 109/L) at the screening visit 

  • Unable or unwilling to undergo the required blood testing 

  • Inability to take or swallow oral medication 

  • Pregnant, breastfeeding or planning to become pregnant during the trial 

  • Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 30 days before the screening assessment, or currently enrolled in an interventional investigational trial 

  • Currently taking any other iron chelator(s), or taken any other iron chelator(s) within three weeks of the screening visit 

  • Currently taking medicines that are known to cause agranulocytosis or are associated with neutropenia 

  • Previous treatment with deferiprone with a serious adverse reaction (SAR) requiring withdrawal of deferiprone 

  • Patients who, in the opinion of the Investigator, represent a high medical or psychological risk

  • Active drug or alcohol use or dependence that, in the opinion of the Investigator, would interfere with adherence to trial requirements 

  • Movement disorder preventing brain imaging 

  • Any other condition which, in the opinion of the Investigator, makes the patient inappropriate for entry into the trial 

Funders and sponsors

Funder: LifeArc

Sponsors: Cambridge University Hospitals NHS Foundation Trust & University of Cambridge

Chief investigator

Chief investigator

Professor Patrick Chinnery

Contact details

Clinical trial coordinator: Kerry Dresser

Email: [email protected]