PKAN: Results of clinical trial with deferiprone
From 2011 to 2015, the international NBIA research project TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration) was funded by the European Union. A key TIRCON sub-project was a clinical study to investigate the safety and efficacy of the iron chelator deferiprone in PKAN patients. This study consisted of two steps:
- a randomized, double-blind, placebo-controlled study of 18 months per patient (pP)
- a subsequent 18-month (pP) open-label extension study for previous study participants.
There were four clinical TIRCON centers in Germany, Italy, England and the USA.
Data from up to 88 patients in the placebo-controlled part of the study and up to 62 patients in the extension study were analyzed. The final patient visit in mid-March 2018 marked the end of the two-stage study, which ran for a total of three years.
Deferiprone was largely well tolerated. Deferiprone-specific side effects included mild to moderate anemia, slightly decreased serum ferritin and mild iron deficiency. This could be treated with iron supplements during the study.
In the first part of the study, the iron concentrations in the globus pallidus of 40 patients were examined using MRI; while these did not change in the placebo group, the amount of iron decreased significantly in the deferiprone group.
Various scales were used for the clinical studies to measure changes over the course of the study. The Barry-Albright Dystonia Scale was the primary endpoint. Secondary endpoints included scales to measure Parkinson's symptoms and factors such as functional independence and quality of life.
Although disease progression continued in all patients during the study period, overall the study showed evidence that deferiprone - in contrast to placebo - can most likely delay disease progression in PKAN patients, especially when considering not only the primary endpoint, the BAD scale, but also the secondary endpoints of the other scales.
This delaying effect of the iron chelator on the clinical course was observed with greater clarity in the subgroup of patients with atypical PKAN and was subsequently confirmed in the extension study. In patients who had received placebo in the randomized part of the study, disease progression was then delayed in the extension study compared to the first 18 months on placebo. The possible positive effect of deferiprone was also reflected in the fact that some patients taking the drug were able to reduce their usual dystonia medication.
Numerous patients with advanced PKAN were included in the study. However, the expected positive effect of medication decreases with increasing neurodegeneration. It should therefore be considered for the future whether earlier use of deferiprone, when there is less damage caused by the iron, could enhance the positive effect in terms of slowing down the progression of the disease.
If you would like to learn more about the study, The Lancet Neurology has published the Summary of the original article. Unfortunately, the full article is not available free of charge online in open access. However, interested parties are welcome to contact info@hoffnungsbaum.de for further information on the article.
