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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)

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 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)


Detailed Summary:
Sponsor: ApoPharma

Current Primary Outcome:

  • 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.


Original Primary Outcome:

  • Change in severity of dystonia (using BAD scale) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: 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: 18 months ]
    Patient Global Impression of Improvement (PGI-I) will be completed at months 6, 12 and 18 visits.


Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

  • Change in globus pallidus iron levels (using MRI T2*) in patients with PKAN treated with deferiprone in comparison to placebo. [ Time Frame: 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: 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: 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: 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: 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.


Information By: ApoPharma

Dates:
Date Received: December 3, 2012
Date Started: December 2012
Date Completion:
Last Updated: March 22, 2017
Last Verified: April 2016