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

NCT ID: NCT01741532

Last Updated: 2019-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-13
• Study Completion Date: 2017-01-11

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).

Detailed Description

This is a multi-center, double-blind, randomized, placebo-controlled, 18-month study in patients with PKAN aged 4 years and older. Participants are randomized in a 2:1 ratio to receive either deferiprone oral solution or placebo, twice a day for 18 months. Efficacy assessments, an MRI scan to measure iron levels in the globus pallidus, pharmacokinetic evaluations, and safety assessments are conducted at specified time points. Following completion of the trial, eligible patients are invited to enroll in an 18-month extension study, TIRCON2012V1-EXT, in which all participants receive deferiprone.

Conditions

Pantothenate Kinase-Associated Neurodegeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Deferiprone

Deferiprone 80 mg/mL oral solution

Group Type: EXPERIMENTAL

Deferiprone oral solution

Intervention Type: 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.

Placebo

Matching placebo solution

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Deferiprone oral solution

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

DFP; L1

Eligibility Criteria

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:

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;

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

ApoPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fernando Tricta, MD

Role: STUDY_CHAIR

ApoPharma Inc.

Thomas Klopstock, MD

Role: PRINCIPAL_INVESTIGATOR

Friedrich-Baur-Institute, Department of Neurology, University of Munich Ziemssenstr

Elliott Vichinsky, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital & Research Center at Oakland Hematology/ Oncology, Pediatric Rehabilitation

Locations

Children's Hospital & Research Center at Oakland

Oakland, California, United States

Klinikum der Universität München

Munich, , Germany

Foundation Neurological Institute C. Besta

Milan, , Italy

Newcastle University Institute of Human Genetics

Newcastle upon Tyne, , United Kingdom

Countries

United States; Germany; Italy; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 31202468 (View on PubMed)

Other Identifiers

1R01FD004103-01

Identifier Type: FDA

Identifier Source: secondary_id

View Link

TIRCON2012V1

Identifier Type: -

Identifier Source: org_study_id