Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration (TIRCON-EXT)

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

Patients with PKAN will be treated with the iron chelator deferiprone for 18 months. Only patients who have completed the earlier study TIRCON2012V1 (NCT01741532), a double-blind placebo-controlled trial in which participants were randomized to receive either deferiprone or placebo for 18 months, are eligible to enroll.

Study Overview

• Status: Completed
• Conditions: Pantothenate Kinase-Associated Neurodegeneration
• Intervention / Treatment: Drug: Deferiprone oral solution

Detailed Description

TIRCON2012V1-EXT is a multi-center, single-arm, open-label study. All patients who completed the earlier study TIRCON2012V1 (NCT01741532) are eligible to take part. In the initial study, patients were randomized in a 2:1 ratio to receive 18 months of treatment with either the iron chelator deferiprone or placebo, respectively. In this extension study, all participants will receive deferiprone for 18 months. Thus, depending on which product was received earlier, patients will be on deferiprone for a total of either 1.5 years or 3 years. As in the earlier study, assessments will be carried out every six months to look at the safety of the drug and to see if patients are showing any improvement in dystonia and other symptoms of PKAN.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 80336
    • Klinikum der Universität München
• Italy
  • Milan, Italy, 20133
    • Foundation Neurological Institute C. Besta
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE1 3BZ
    • Newcastle University Institute of Human Genetics
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Completed study TIRCON2012V1

Exclusion Criteria:

• Withdrew from the study TIRCON2012V1 for reasons of safety
• Plan to participate in another clinical trial at any time from the day of enrolment until 30 days post-treatment in the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferiprone; All patients will receive deferiprone oral solution.	Drug: Deferiprone oral solution; Deferiprone oral solution at a dosage of up to 15 mg per kilogram of body weight, twice a day; Other Names: DFP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Safety and tolerability were assessed based on changes in: frequency of adverse events (AEs), frequency of serious adverse events (SAEs), and discontinuation due to AEs. No statistical comparison between the groups was conducted as all participants received the same study product.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study	The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of both the initial study (during which one group received placebo and the other received deferiprone) and the extension study (during which both groups received deferiprone).	Baseline and Month 18 of each study
Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies	The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of each study.	Baseline and Month 18 of each study
Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies	The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of the study.	Baseline and Month 18 of each study
Proportion of Patients With Improved or Unchanged BAD Score	Patients were deemed to be responders if their BAD total score either improved or remained unchanged from baseline, with baseline being the start of each study for the placebo-DFP group and the start of the initial study for the DFP-DFP group	Month 18 of each study
Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies	The Patient Global Impression of Improvement (PGI-I) is a global index used to rate the response of a condition to a therapy. Patients were asked at each post-baseline visit to rate their overall condition since the start of the extension study on a 7-point rating scale: 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 of each study

Collaborators and Investigators

• Sponsor: ApoPharma
• Investigators: Principal Investigator: Thomas Klopstock, MD, Klinikum der Universität München; Principal Investigator: Nardo Nardocci, MD, Foundation Neurological Institute C. Besta; Principal Investigator: Patrick Chinnery, MD, Newcastle University Institute of Human Genetics

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): March 16, 2018
• Study Completion (Actual): March 16, 2018

Study Registration Dates

• First Submitted: June 5, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 26, 2014

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Ferriprox; Deferiprone; Neurodegeneration with Brain Iron Accumulation; NBIA; PKAN; Pantothenate Kinase-Associated Neurodegeneration
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neuroaxonal Dystrophies; Pantothenate Kinase-Associated Neurodegeneration; Nerve Degeneration; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: TIRCON2012V1-EXT; 2012-000845-11 (EudraCT Number)