Clinical trial NCT01741532: Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
Official title: A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pantothenate Kinase-Associated Neurodegeneration
Keywords: Pantothenate Kinase-associated Neurodegeneration
PKAN
NBIA
Deferiprone
Ferriprox
Neurodegeneration with brain iron accumulation
Lead sponsor: ApoPharma
Sponsor class: INDUSTRY
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2012-12-05
Enrollment: 89
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

Primary outcomes:
measure: Change in Score on Barry-Albright Dystonia Scale
timeFrame: Baseline to 18 Months
measure: Score on Patient Global Impression of Improvement at End of Study
timeFrame: Month 18
Secondary outcomes:
measure: Change in Score on Unified Parkinson's Disease Rating Scale
timeFrame: Baseline to 18 Months
measure: Change in Score on Functional Independence Measure
timeFrame: Baseline to 18 Months
measure: Change in Score on WeeFIM
timeFrame: Baseline to 18 Months
measure: Change in Score on Pediatric Quality of Life
timeFrame: Baseline to 18 Months
measure: Change in Score on Pittsburgh Sleep Quality Index
timeFrame: Baseline to 18 Months
measure: Change in Level of Brain Iron
timeFrame: Baseline to 18 Months
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital & Research Center at Oakland
state: California
city: Munich
country: Germany
facility: Klinikum der Universität München
city: Milan
country: Italy
facility: Foundation Neurological Institute C. Besta
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle University Institute of Human Genetics
Study officials:
affiliation: ApoPharma Inc.
name: Fernando Tricta, MD
role: STUDY_CHAIR
affiliation: Friedrich-Baur-Institute, Department of Neurology, University of Munich Ziemssenstr
name: Thomas Klopstock, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital & Research Center at Oakland Hematology/ Oncology, Pediatric Rehabilitation
name: Elliott Vichinsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Klopstock T, Tricta F, Neumayr L, Karin I, Zorzi G, Fradette C, Kmiec T, Buchner B, Steele HE, Horvath R, Chinnery PF, Basu A, Kupper C, Neuhofer C, Kalman B, Dusek P, Yapici Z, Wilson I, Zhao F, Zibordi F, Nardocci N, Aguilar C, Hayflick SJ, Spino M, Blamire AM, Hogarth P, Vichinsky E. Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study. Lancet Neurol. 2019 Jul;18(7):631-642. doi: 10.1016/S1474-4422(19)30142-5.