We were involved in a series of clinical trials called DevelopAKUre, 2012 to 2019. These were designed to determine if a drug, called nitisinone, could help patients with alkaptonuria (AKU).
The DevelopAKUre programme was a series of major international clinical trials, run by a consortium of 12 European partners. It aimed to study a drug, called nitisinone, and assess its effectiveness in treating AKU. Nitisinone is not licensed for AKU but is been used by many patients off-label and at the National Alkaptonuria Centre (NAC) in Liverpool. Those patients experience benefit, but the only way to be certain a drug works is through clinical research.
In July 2019 we were informed that the results from SONIA 2 were positive and SOBI (Swedish Orphan Biovitrum
) , who make the drug will be applying for market authorisation for a license for the drug to be used in AKU patients. If successful, this should theoretically mean Nitisinone can be prescribed to AKU patients across Europe.
The trials were split into 3 parts:
SONIA 1 (Suitability of Nitisinone In Alkaptonuria 1) was designed to ascertain the correct and most effective amount of nitisinone patients should take to reduce levels of homogentistic acid (HGA) - this is called dosage.
SONIA 1 finished In June 2014 and the main scientific paper was published in December 2014. It found that levels of HGA are reduced by nitisinone and this is dependent on dosage levels. You can view the academic paper with results here.
SONIA 2 (Suitability of Nitisinone In Alkaptonuria 2) was designed to test the safety and whether nitisinone slows down the damage HGA does to the body of AKU patients.
SONIA 2 recruited 138 patients over 3 trial sites in Liverpool, UK; Paris, France and Piešťany, Slovakia. The trial took place over 4 years and required patients to make up to 6 trips to their nearest trial site. The patients were split into two groups of 69 with one group taking nitisinone and one not taking nitisinone. This was important as it allows us to show the positive effect of nitisinone. SONIA 2 highlighted positive trends in when nitisinone was used to treat AKU. This led to SOBI deciding to apply to the EMA for market authorisation.
SOFIA (Subclinical Ochronotic Features in Alkaptonuria) was designed to compare AKU patients from different age groups to study when symptoms start to present. The study enabled us to understand at what age AKU patients need to start taking nitisinone to best combat the damaging effects of the disease.
SOFIA tested patients for Ochronosis, the process where cartilage is discoloured black by the effects of AKU. This is thought to be the earliest sign of the more damaging symptoms of AKU. SOFIA recruited 32 patients from a range of 7 age groups from 16 to 50+. The study required one visit to the Royal Liverpool University Hospital.
SOFIA’s findings led the AKU Society to want to understand AKU in children under 16. We have begun to find funding for a SOFIA- pediatric study. More information can be found here.
The SOFIA paediatric is not part of DevelopAKure.