efficacy and safety study of deferiprone in patients with pantothenate kinase-associated neurodegeneration (pkan)

Conditions: Pantothenate Kinase-Associated Neurodegeneration

Summary: a multi-center, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with pkan. this investigator-initiated trial was funded by the european commission's seventh framework programme (fp7/2007-2013, health-f2-2011, grant agreement no. 277984) to the tircon consortium (treat iron-related childhood-onset neurodegeneration) and by the fda office of orphan products development (oopd) (dr. elliott vichinsky).

this is a multi-center, double-blind, randomized, placebo-controlled, 18-month study in patients with pkan aged 4 years and older. participants are randomized in a 2:1 ratio to receive either deferiprone oral solution or placebo, twice a day for 18 months. efficacy assessments, an mri scan to measure iron levels in the globus pallidus, pharmacokinetic evaluations, and safety assessments are conducted at specified time points. following completion of the trial, eligible patients are invited to enroll in an 18-month extension study, tircon2012v1-ext, in which all participants receive deferiprone.

Eligibility criteria:
main inclusion criteria: * males or females 4 years of age and older at screening visit; * have pkan, confirmed by genetic testing (supporting evidence required); * barry-albright dystonia (bad) total score ≥ 3 at the screening visit; * patients who have deep brain stimulation (dbs) systems or baclofen pumps in place will be eligible for the study, but they must have had a stable setting for at least two months prior to the screening visit and stimulation parameters / pump settings must remain stable for the duration of the trial: main exclusion criteria: * evidence of iron deficiency defined by fe:tibc ratio \<15%, or serum ferritin \<12 ng/ml; * treatment with deferiprone in the past 12 months; * previous failure of treatment with deferiprone, or previous discontinuation of treatment with deferiprone due to adverse events; * conditions known to contraindicate the use of deferiprone (history of agranulocytosis or recurrent episodes of neutropenia); * a serious, unstable chronic illness not related to pkan condition during the past 3 months before screening visit including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease; * evidence of abnormal liver or renal function (serum liver enzyme level(s) \> 3 times upper limit of normal at screening) or abnormal creatinine levels at screening visit; * disorders associated with neutropenia (anc \< 1.5 x 10\^9/l) or thrombocytopenia (platelet count \< 50 x 10\^9/l) in the 12 months preceding the initiation of the study medication. exception: for patients whose neutropenia was attributed by the treating physician to episodes of infection or to drugs associated with a decline in the neutrophil count and in whom the anc has fully recovered at the screening visit; * history of malignancy; other protocol inclusion or exclusion criteria may apply.

Keywords: pantothenate kinase-associated neurodegeneration pkan nbia deferiprone ferriprox neurodegeneration with brain iron accumulation