Overview

This trial is active, not recruiting.

Condition pantothenate kinase-associated neurodegeneration
Treatments deferiprone oral solution, placebo oral solution
Phase phase 3
Sponsor ApoPharma
Start date December 2012
End date September 2016
Trial size 89 participants
Trial identifier NCT01741532, 1R01FD004103-01, TIRCON2012V1

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)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
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.
deferiprone oral solution DFP
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.
(Placebo Comparator)
A deferiprone matching placebo oral solution will be given twice daily for 18 months.
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.

Primary Outcomes

Measure
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
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

Secondary Outcomes

Measure
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
Change in motor symptoms (using UPDRS) in patients with PKAN treated with deferiprone in comparison to placebo.
time frame: Baseline to 18 months
Change in quality of life (PedsQL) in patients with PKAN treated with deferiprone in comparison to placebo.
time frame: Baseline to 18 months
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
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
Safety and tolerability of deferiprone in patients with PKAN.
time frame: 18 months
Steady state pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite.
time frame: 12 hours at month 6 visit

Eligibility Criteria

Male or female participants at least 4 years old.

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.

Additional Information

Official title A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
Principal investigator Thomas Klopstock, MD
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by ApoPharma.