Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
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|ClinicalTrials.gov Identifier: NCT01741532|
Recruitment Status : Completed
First Posted : December 5, 2012
Results First Posted : May 23, 2019
Last Update Posted : July 5, 2019
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).
|Condition or disease||Intervention/treatment||Phase|
|Pantothenate Kinase-Associated Neurodegeneration||Drug: Deferiprone oral solution Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||89 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Placebo solution matched deferiprone oral solution in appearance, taste, and packaging|
|Official Title:||A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)|
|Actual Study Start Date :||December 13, 2012|
|Actual Primary Completion Date :||October 21, 2016|
|Actual Study Completion Date :||January 11, 2017|
Deferiprone 80 mg/mL oral solution
Drug: Deferiprone oral solution
Deferiprone 80 mg/mL oral solution will be administered twice daily (b.i.d.) for 18 months. An initial dose of 5 mg/kg b.i.d. will be administered for 6 weeks. The dose will then be escalated to 10 mg/kg b.i.d. and finally to 15 mg/kg b.i.d.
Placebo Comparator: Placebo
Matching placebo solution
A deferiprone matching placebo oral solution will be given twice daily for 18 months.
- Change in Score on Barry-Albright Dystonia Scale [ Time Frame: Baseline to 18 Months ]The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.
- Score on Patient Global Impression of Improvement at End of Study [ Time Frame: Month 18 ]The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
- Change in Score on Unified Parkinson's Disease Rating Scale [ Time Frame: Baseline to 18 Months ]The Unified Parkinson's Disease Rating Scale (UPDRS) is the major rating scale used to assess severity of symptoms of Parkinson's disease, some of which are similar to those of PKAN. The UPDRS subscales used in this study were Part I: Mentation, Behavior and Mood, scored from 0 (best) to 16 (worst); Part II: Activities of Daily Living, scored from 0 (best) to 52 (worst); Part III: Motor Examination, scored from 0 (best) to 108 (worst); and Part VI: Schwab and England Activities of Daily Living Scale, scored from 0% (worst) to 100% (best).
- Change in Score on Functional Independence Measure [ Time Frame: Baseline to 18 Months ]The Functional Independence Measure (FIM) scale is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).
- Change in Score on WeeFIM [ Time Frame: Baseline to 18 Months ]The WeeFIM is the pediatric version of the Functional Independence Measure scale, and is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).
- Change in Score on Pediatric Quality of Life [ Time Frame: Baseline to 18 Months ]The Pediatric Quality of Life (PedsQL) questionnaire is used to measure functional health and well-being from the patient's point of view. Separate versions of the questionnaire are available for children, young adults aged 18-25 years, and adults older than 25 years. Patients are asked to indicate how they have felt over the past month, and the scores of the 23 questions are used to generate an overall score that ranges from 0 (worst) to 100 (best).
- Change in Score on Pittsburgh Sleep Quality Index [ Time Frame: Baseline to 18 Months ]The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A total of 19 individual items are used to generate 7 "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, and a score is generated that ranges from 0 (best) to 21 (worst).
- Change in Level of Brain Iron [ Time Frame: Baseline to 18 Months ]Neurodegeneration in patients with PKAN is associated with localized brain iron accumulation, with the highest amount of accumulation seen in the globus pallidus, one of the main areas for motor control. MRI R2* scans of this region were performed at baseline and Month 18 in a subset of patients who did not have a deep brain stimulation (DBS) device implanted, and for whom the use of anesthesia, if required, was deemed acceptable by the investigator.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01741532
|United States, California|
|Children's Hospital & Research Center at Oakland|
|Oakland, California, United States, 94609|
|Klinikum der Universität München|
|Munich, Germany, 80336|
|Foundation Neurological Institute C. Besta|
|Milan, Italy, 20133|
|Newcastle University Institute of Human Genetics|
|Newcastle Upon Tyne, United Kingdom, NE1 3BZ|
|Study Chair:||Fernando Tricta, MD||ApoPharma Inc.|
|Principal Investigator:||Thomas Klopstock, MD||Friedrich-Baur-Institute, Department of Neurology, University of Munich Ziemssenstr|
|Principal Investigator:||Elliott Vichinsky, MD||Children's Hospital & Research Center at Oakland Hematology/ Oncology, Pediatric Rehabilitation|