PKAN: Results of Clinical Trial with Deferiprone

from | July 17, 2019

From 2011 to 2015, the international NBIA research project TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration) received financial support from the European Union. A major TIRCON subproject was a clinical trial to investigate the safety and efficacy of the iron chelator deferiprone in PKAN patients. This study consisted of two steps:

  1. a randomized, double-blind, placebo-controlled trial of 18 months per patient (pP)
  2. a subsequent 18-month (pP) open-label extension study for previous study participants.

There were four TIRCON clinical centers in Germany, Italy, England and the USA.

Data from up to 88 patients in the placebo-controlled part of the study and from up to 62 patients in the extension study were evaluated. With the last patient visit in mid-March 2018, the two-stage study, which ran for a total of three years, was completed.

For the most part, deferiprone was well tolerated. Deferiprone-specific side effects included mild to moderate anaemia, mildly 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 with MRI. While these did not change in the group of patients with placebo, the amount of iron decreased significantly in the deferiprone group.

For the clinical examinations, different scales were used to measure changes in the course of the study. The Barry-Albright dystonia scale was the primary endpoint. In addition, secondary endpoints included scales to measure Parkinson's symptoms and factors such as functional independence or quality of life.

Although the disease progressed in all patients during the study period, the study as a whole found evidence that deferipron, as opposed to placebo, is highly likely to delay disease progression in PKAN patients, especially when not only the primary endpoint, the BAD scale, is taken into account, 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 subsequently confirmed in the extension study. In patients who received placebo in the randomized part of the study, the course of the disease was then delayed in the extension study compared to the first 18 months with placebo. The possible positive effect of deferiprone was also expressed in the fact that patients who took the drug were able to reduce their usual dystonia medication in some cases.

The study included a large number of patients with advanced PKAN. However, as neurodegeneration increases, the expected positive effect of medication decreases. Therefore, it should be considered for the future whether earlier use of deferiprone, if there is even less damage caused by iron, could not increase the positive effect in terms of slowing down the progression of the disease.

If you want to learn more about the study, you can find the following information at The Lancet Neurology. Summary of the original English article. Unfortunately, the full article is not available online for free in Open Access. However, interested parties are welcome to contact for further information on the article.

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