Efficacy and Safety Study of Fosmetpantotenate (RE-024) in PKAN Participants

Pantothenate Kinase-Associated Neurodegeneration Clinical Trial

— PKAN  

Official title:

Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), a Phosphopantothenate Replacement Therapy, in Pantothenate Kinase-Associated Neurodegeneration (PKAN) Patients: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03041116
• Other study ID #: 024PKAN15004
• Status: Terminated
• Phase: Phase 3
• Start date: July 17, 2017
• Est. completion date: December 30, 2019

Study information

• Verified date: January 2021
• Source: Travere Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study investigated whether fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy, was safe and effective in treating participants with PKAN.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 84
• Est. completion date: December 30, 2019
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

Inclusion Criteria:

1. The participant had a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 gene.

2. The participant was male or female aged 6 to 65 years, inclusive.

3. The participant had a score of = 6 on the PKAN-specific activities of daily living measure.

Exclusion Criteria:

1. The participant had required regular or intermittent invasive ventilatory support to maintain vital signs within 24 weeks prior to randomization.

2. The participant had a deep brain stimulation device implanted within 6 months prior to screening.

3. The participant had taken deferiprone within 30 days prior to screening.

4. The participant was unable to maintain stable doses of allowed concomitant medications for the first 24 weeks of the study.

Related Conditions & MeSH terms

• Nerve Degeneration
• Pantothenate Kinase-Associated Neurodegeneration

Intervention

Drug:
• Fosmetpantotenate
Daily dosing
• Placebo
Daily dosing

Locations

Country	Name	City	State
Canada	Travere Investigational Site	Toronto	Ontario
Canada	Travere Investigational Site	Toronto	Ontario
Czechia	Travere Investigational Site	Praha 2	NAP
France	Travere Investigational Site	Montpellier	Languedoc-Rousillon
France	Travere Investigational Site	Paris	Ile-de-France
Germany	Travere Investigational Site	München	Bavaria
Italy	Travere Investigational Site	Milano
Norway	Travere Investigational Site	Oslo
Poland	Travere Investigational Site	Warsaw
Spain	Travere Investigational Site	Barcelona	Catalonia
Spain	Travere Investigational Site	Barcelona
United States	Travere Investigational Site	Boston	Massachusetts
United States	Travere Investigational Site	Chicago	Illinois
United States	Travere Investigational Site	Decatur	Georgia
United States	Travere Investigational Site	Houston	Texas
United States	Travere Investigational Site	Irvine	California
United States	Travere Investigational Site	Miami	Florida
United States	Travere Investigational Site	New York	New York
United States	Travere Investigational Site	Pittsburgh	Pennsylvania
United States	Travere Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Travere Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  France,  Germany,  Italy,  Norway,  Poland,  Spain, 

References & Publications (1)

Klopstock T, Escolar ML, Marshall RD, Perez-Dueñas B, Tuller S, Videnovic A, Greblikas F. The FOsmetpantotenate Replacement Therapy (FORT) randomized, double-blind, Placebo-controlled pivotal trial: Study design and development methodology of a novel prim — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline In The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living (PKAN-ADL) Total Score To The End Of The 24-week Double-blind Period	Change from baseline to Week 24 activities of daily living was assessed on the PKAN-ADL scale based on the Unified Parkinson's Disease Rating Scale (UPDRS) Part II. The PKAN-ADL is a validated measure of the participant's ability to complete ADL that are impacted by the diffuse motor manifestations of PKAN. It consists of 12 items related to activities of daily living, including eating, dressing, and walking. Each item has responses ranging from 0-4, with a higher value indicating greater disability in the given activity. To compute the total score, responses are summed across the 12 items. The available range of total scores on the PKAN-ADL scale was from 0 (no ADL affected) to 48 (ADL highly affected). The reported least square mean (LSM) was adjusted for baseline score and age group from the Type III analysis. A decrease in score indicates improvement in symptoms.	Baseline (Day -1), Week 24
Primary	Number Of Participants With At Least 1 (=1) Treatment-emergent Adverse Event (TEAE) And Treatment-emergent Serious Adverse Event (TESAE) During The 24-week Double-blind Period	An adverse event (AE) is any untoward medical occurrence associated with the use of the investigational product (IP; active or placebo) in a participant, without regard to possibility of causal relationship with IP. A serious adverse event (SAE) is an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of death from AE); persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious medical events. The TEAEs in the double-blind period are defined as AEs that are new or are a worsening of an existing condition that begins from day of first dose of IP until day after last dose for double-blind treatment period.	From Screening until end of Week 24
Secondary	Absolute Change From Baseline In The UPDRS Part 3 (UPDRS-III) Total Score To The End Of The 24-week Double-blind Period	The UPDRS is a comprehensive assessment of the burden and severity of signs and symptoms of Parkinsonism captured via systematic interview and neurological examination. The UPDRS-III is a standardized neurological examination that evaluates the performance of movements commonly affected in Parkinson's disease, PKAN, and other movement disorders. Part III of the UPDRS consists of 27 items, which correspond to 14 domains related to motor abilities such as tremor, stability, and bradykinesia. Each item has responses ranging from 0-4. To compute the UPDRS-III total score, responses are summed across the 27 items, and accordingly, range from 0-108. For domain totals, responses are summed across all of the items in a given domain (when domain corresponds to multiple items). An increase in score indicates greater disability. The reported LSM was adjusted for baseline score and age group from the Type III analysis.	Baseline (Day -1), Week 24

External Links

•   Poster presented at the Child Neurology Society Annual Meeting in Chicago, Illinois, October 2018
•   Study website