Interest in iron chelation has reemerged as data on deferiprone (Ferriprox®) have accumulated in several patient populations. Iron chelating agents have been tried in the past without clear benefit. Until recently, trials were limited by the development of systemic iron deficiency before any clinical neurologic benefits were evident. Unlike earlier drugs, deferiprone crosses the blood-brain barrier and removes intracellular iron.
A clinical trial is underway to investigate if the iron-chelating drug deferiprone can remove brain iron by oral (taken by mouth) medication. Clinical examinations during the study shall explore if deferiprone has an impact on the course of pantothenate kinase-associated neurodegeneration (PKAN), a form of NBIA.
The drug will be tested for 18 months in 90 patients. The study will be carried out at five centers: Munich (Germany), Warsaw (Poland), Milan (Italy), Newcastle (United Kingdom) and Oakland (California in the United States).
It’s a gold standard study: randomized, double-blind and placebo-controlled. “Placebo-controlled” means that in the context of this study, deferiprone will be compared with a placebo. A placebo looks identical to the deferiprone but does not contain any active ingredient. The study participants will have a two in three chance of getting deferiprone and a one in three chance of getting the placebo. The selection will be done by randomization.
“Randomization” is done according to a computer generated randomization list. Every patient would be allocated to either placebo or deferiprone group according to this list. It is necessary to compare the drug with a placebo group to fully assess the effects and side effects of deferiprone.
“Double-blinding” means that neither the patient nor the physicians know in which group the patient is in. This is necessary for an objective collection of study data.
The study participants will be ages 4 to adult and must have PKAN disease, confirmed by genetic testing.
Nancy Sweeters, study coordinator for the U.S. site at the Children’s Hospital and Research Center Oakland, says that the screening process involves signing a simplified informed consent form that allows the release of some medical information. That information will include the lab confirmation of a genetic diagnosis of PKAN, medical history, current medications and results of a complete blood count taken in the past year.
Led by Dr. Elliott Vichinsky at the U.S. site, the Phase III trial plans to enroll 40. The other sites in Europe will enroll another 50 patients for a total of 90.
The European Union is funding the study in the U.S. and Europe through a grant called Treat Iron-Related Childhood-Onset Neurodegeneration or TIRCON. Additionally, the U.S. Food and Drug Administration is funding a portion of the study in the U.S. The pharmaceutical company, ApoPharma Inc., is providing the deferiprone and placebo for all of the sites and is the contract research organization that will monitor the study.
U.S. participants will be required to travel to Oakland six times during the trial with transportation and lodging provided for each visit.
If trial results are positive, all participants will be offered deferiprone on a compassionate-use basis at no cost. In the U.S. that will last until the FDA approves the drug for PKAN.
U.S. Clinical Trial Center:
Children’s Hospital & Research Center Oakland
Dr. Elliott Vichinsky, PI
Nancy Sweeters, Study coordinator