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

NCT01741532 | Completed Phase 3 Results DMC

• 2 other identifiers: TIRCON2012V11R01FD004103-01
• Study Type: interventional
• Target: 89
• Locations: 4 countries
• Sites: 4

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 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).

Conditions

Pantothenate Kinase-Associated Neurodegeneration

Keywords

Pantothenate Kinase-associated Neurodegeneration; PKAN; NBIA; Deferiprone; Ferriprox; Neurodegeneration with brain iron accumulation

Outcome Measures

Primary Outcomes (2)

• Change in Score on Barry-Albright Dystonia Scale

  The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.

  Baseline to 18 Months

• Score on Patient Global Impression of Improvement at End of Study

  The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

  Month 18

Secondary Outcomes (6)

• Change in Score on Unified Parkinson's Disease Rating Scale

  Baseline to 18 Months

• Change in Score on Functional Independence Measure

  Baseline to 18 Months

• Change in Score on WeeFIM

  Baseline to 18 Months

• Change in Score on Pediatric Quality of Life

  Baseline to 18 Months

• Change in Score on Pittsburgh Sleep Quality Index

  Baseline to 18 Months

Study Arms (2)

Deferiprone

EXPERIMENTAL

Deferiprone 80 mg/mL oral solution

Drug: Deferiprone oral solution

Placebo

PLACEBO COMPARATOR

Matching placebo solution

Drug: Placebo

Interventions

Deferiprone oral solution DRUG

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.

Also known as: DFP, L1

Deferiprone

Placebo DRUG

A deferiprone matching placebo oral solution will be given twice daily for 18 months.

Placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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;

Sponsors & Collaborators

• ApoPharma: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (4)

Children's Hospital & Research Center at Oakland

Oakland, California, 94609, United States

Location

Klinikum der Universität München

Munich, 80336, Germany

Location

Foundation Neurological Institute C. Besta

Milan, 20133, Italy

Location

Newcastle University Institute of Human Genetics

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Location

Related Publications (1)

• Klopstock T, Tricta F, Neumayr L, Karin I, Zorzi G, Fradette C, Kmiec T, Buchner B, Steele HE, Horvath R, Chinnery PF, Basu A, Kupper C, Neuhofer C, Kalman B, Dusek P, Yapici Z, Wilson I, Zhao F, Zibordi F, Nardocci N, Aguilar C, Hayflick SJ, Spino M, Blamire AM, Hogarth P, Vichinsky E. Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study. Lancet Neurol. 2019 Jul;18(7):631-642. doi: 10.1016/S1474-4422(19)30142-5.

  PMID: 31202468 DERIVED

MeSH Terms

Conditions

Pantothenate Kinase-Associated Neurodegeneration

Interventions

Deferiprone; Isoflurophate; Long Interspersed Nucleotide Elements

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroaxonal Dystrophies; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organofluorophosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Retroelements; Interspersed Repetitive Sequences; Repetitive Sequences, Nucleic Acid; Base Sequence; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genome Components; Genome

Results Point of Contact

• Title: Caroline Fradette
• Organization: ApoPharma Inc.

cfradett@apopharma.com

416-401-7543

Study Officials

• Fernando Tricta, MD

  ApoPharma Inc.

  STUDY CHAIR

• 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 Hematology/ Oncology, Pediatric Rehabilitation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo solution matched deferiprone oral solution in appearance, taste, and packaging
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2012
• First Posted: December 5, 2012
• Study Start: December 13, 2012
• Primary Completion: October 21, 2016
• Study Completion: January 11, 2017
• Last Updated: July 5, 2019
• Results First Posted: May 23, 2019

Record last verified: 2019-06

Locations

DE (1); IT (1); GB (1); US (1)