This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

A Two-arm Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ApoPharma
ClinicalTrials.gov Identifier:
NCT01741532
First received: December 3, 2012
Last updated: March 22, 2017
Last verified: April 2016
  Purpose

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 is 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 OOPD (Dr. Elliott Vichinsky)


Condition Intervention Phase
Pantothenate Kinase-Associated Neurodegeneration Drug: Deferiprone oral solution Drug: Placebo oral solution Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)

Resource links provided by NLM:


Further study details as provided by ApoPharma:

Primary Outcome Measures:
  • Change in severity of dystonia (using BAD scale) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 Months ]
    The Barry-Albright Dystonia Scale (BAD) will be completed at baseline, months 6, 12 and 18 visits and will be assessed by central raters.

  • Change in patient's global impression of condition's improvement (using PGI-I) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 months ]
    Patient Global Impression of Improvement (PGI-I) will be completed at months 6, 12 and 18 visits.


Secondary Outcome Measures:
  • Change in globus pallidus iron levels (using MRI T2*) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 months ]
    MRI T2* assessments will be completed at the baseline and month 18 visits.

  • Change in motor symptoms (using UPDRS) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 months ]
    Unified Parkinson's Disease Rating Scale (UPDRS) will be completed at the baseline, months 6, 12, and 18 visits.

  • Change in quality of life (PedsQL) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 months ]
    Pediatric Quality of Life Inventory (PedsQL) will be completed at the baseline, months 6, 12 and 18 visits.

  • Change in patient's quality of sleep (using PSQI) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 months ]
    Pittsburgh Sleep Quality Index (PSQI) will be completed at the baseline, months 6, 12 and 18 visits.

  • Change in the measure of functional independence (using WeeFIM or FIM) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: Baseline to 18 months ]
    WeeFIM or FIM will be completed at the baseline, months 6, 12 and 18 visits.

  • Safety and tolerability of deferiprone in patients with PKAN. [ Time Frame: 18 months ]
    Safety and tolerability will be assessed based on changes in: frequency of adverse events (AEs), frequency of serious adverse events (SAEs), discontinuation due to AEs, clinical laboratory tests (including hematology and biochemistry)and ECG from baseline to month 18.

  • Steady state pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite. [ Time Frame: 12 hours at month 6 visit ]
    Pharmacokinetics steady state standard parameters will be assessed in a subset of up to 24 patients over a 12 hour dosing interval using individual serum concentration-time profiles of deferiprone and its 3-O-glucuronide metabolite.


Enrollment: 89
Study Start Date: December 2012
Study Completion Date: January 11, 2017
Primary Completion Date: October 7, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deferiprone
Deferiprone 80 mg/mL oral solution will be administered twice daily for 18 months. An initial dose 5 mg/kg/day will be administered for 6 weeks. Dose will then be escalated to 10mg/kg BID and finally to 15 mg/kg BID.
Drug: Deferiprone oral solution
Deferiprone oral solution will be given twice daily for 18 months. Dose will be escalated every 6 weeks starting at 5mg/kg, and increasing to 10mg/kg and finally 15 mg/kg.
Other Names:
  • DFP
  • Ferriprox
  • L1
Placebo Comparator: Deferiprone matching placebo
A deferiprone matching placebo oral solution will be given twice daily for 18 months.
Drug: Placebo oral solution
Placebo oral solution will be given twice daily for 18 months. Dose will be escalated every 6 weeks starting at 5mg/kg, and increasing to 10mg/kg and finally 15 mg/kg.

  Eligibility

Ages Eligible for Study:   4 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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);
  • 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 10E9/L) or thrombocytopenia (platelet count < 50 x 10E9/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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01741532

Locations
United States, California
Children's Hospital & Research Center at Oakland
Oakland, California, United States, 94609
Germany
Klinikum der Universität München
Munich, Germany, 80336
Italy
Foundation Neurological Institute C. Besta
Milan, Italy, 20133
United Kingdom
Newcastle University Institute of Human Genetics
Newcastle Upon Tyne, United Kingdom, NE1 3BZ
Sponsors and Collaborators
ApoPharma
Investigators
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 Haematology/ Oncology, Peadiatric Rehabilitation
  More Information

Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT01741532     History of Changes
Other Study ID Numbers: TIRCON2012V1
1R01FD004103-01 ( US NIH Grant/Contract Award Number )
Study First Received: December 3, 2012
Last Updated: March 22, 2017

Keywords provided by ApoPharma:
Pantothenate Kinase-associated Neurodegeneration
PKAN
NBIA
Deferiprone
Ferriprox

Additional relevant MeSH terms:
Nerve Degeneration
Pantothenate Kinase-Associated Neurodegeneration
Brain Diseases
Iron Chelating Agents
Pathologic Processes
Basal Ganglia Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroaxonal Dystrophies
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Pharmaceutical Solutions
Deferiprone
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 23, 2017