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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by ApoPharma
Sponsor:
Information provided by (Responsible Party):
ApoPharma
ClinicalTrials.gov Identifier:
NCT01741532
First received: December 3, 2012
Last updated: April 24, 2014
Last verified: April 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 90
Study Start Date: December 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: May 2015 (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
Genders Eligible for Study:   Both
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 Recruiting
Oakland, California, United States, 94609
Contact: Elliott Vichinsky, MD    510-428-3651    EVichinsky@mail.cho.org   
Principal Investigator: Elliott Vichinsky, MD         
Germany
Klinikum der Universität München Recruiting
Munich, Germany, 80336
Contact: Thomas Klopstock, MD    49-89-5160-7474    thomas.klopstock@med.uni-muenchen.de   
Principal Investigator: Thomas Klopstock, MD         
Italy
Foundation Neurological Institute C. Besta Recruiting
Milan, Italy, 20133
Contact: Nardo Nardocci, MD    39-02-23-941    nnardocci@istituto-besta.it   
Principal Investigator: Nardo Nardocci, MD         
United Kingdom
Newcastle University Institute of Human Genetics Recruiting
Newcastle Upon Tyne, United Kingdom, NE1 3BZ
Contact: Patrick Chinnery, MD    44 (0) 191 241 8611    patrick.chinnery@ncl.ac.uk   
Principal Investigator: Patrick Chinnery, MD         
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

No publications provided

Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT01741532     History of Changes
Other Study ID Numbers: TIRCON2012V1, 1R01FD004103-01
Study First Received: December 3, 2012
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Pantothenate Kinase-Associated Neurodegeneration
Nerve Degeneration
Brain Diseases
Iron Chelating Agents
Basal Ganglia Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroaxonal Dystrophies
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Pathologic Processes
Deferiprone
Vitamin B Complex
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014