Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
Condition: Pantothenate Kinase-Associated Neurodegeneration
MeSH terms: Pantothenate Kinase-Associated Neurodegeneration; Nerve Degeneration
Intervention: Deferiprone oral solution; Placebo
Intervention description: 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.; A deferiprone matching placebo oral solution will be given twice daily for 18 months.
Intervention MeSH terms: Deferiprone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
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
Enrollment: 89.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: Pantothenate Kinase-associated Neurodegeneration; PKAN; NBIA; Deferiprone; Ferriprox; Neurodegeneration with brain iron accumulation

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).
    

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.