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

NCT03041116 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 024PKAN15004
• Study Type: interventional
• Target: 84
• Locations: 9 countries
• Sites: 20

Brief Summary

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

Conditions

Pantothenate Kinase-Associated Neurodegeneration

Keywords

PKAN

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Absolute Change From Baseline In The UPDRS Part 3 (UPDRS-III) Total Score To The End Of The 24-week Double-blind Period

  Baseline (Day -1), Week 24

Study Arms (2)

Fosmetpantotenate

EXPERIMENTAL

Administered as powder for reconstitution.

Drug: Fosmetpantotenate

Placebo

PLACEBO COMPARATOR

Administered as powder for reconstitution.

Drug: Placebo

Interventions

Fosmetpantotenate DRUG

Daily dosing

Also known as: RE-024

Fosmetpantotenate

Placebo DRUG

Daily dosing

Placebo

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant had a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 gene.
• The participant was male or female aged 6 to 65 years, inclusive.
• The participant had a score of ≥ 6 on the PKAN-specific activities of daily living measure.

You may not qualify if:

• The participant had required regular or intermittent invasive ventilatory support to maintain vital signs within 24 weeks prior to randomization.
• The participant had a deep brain stimulation device implanted within 6 months prior to screening.
• The participant had taken deferiprone within 30 days prior to screening.
• The participant was unable to maintain stable doses of allowed concomitant medications for the first 24 weeks of the study.

Sponsors & Collaborators

• Travere Therapeutics, Inc.: lead

Study Sites (20)

Travere Investigational Site

Irvine, California, 92697, United States

Location

Travere Investigational Site

Washington D.C., District of Columbia, 20010, United States

Location

Travere Investigational Site

Miami, Florida, 33155, United States

Location

Travere Investigational Site

Decatur, Georgia, 30033, United States

Location

Travere Investigational Site

Chicago, Illinois, 60612, United States

Location

Travere Investigational Site

Boston, Massachusetts, 02114, United States

Location

Travere Investigational Site

New York, New York, 10032, United States

Location

Travere Investigational Site

Pittsburgh, Pennsylvania, 15224, United States

Location

Travere Investigational Site

Houston, Texas, 77030, United States

Location

Travere Investigational Site

Toronto, Ontario, M5G1X8, Canada

Location

Travere Investigational Site

Toronto, Ontario, M5T 2S8, Canada

Location

Travere Investigational Site

Prague, NAP, 12821, Czechia

Location

Travere Investigational Site

Montpellier, Languedoc-Rousillon, France

Location

Travere Investigational Site

Paris, Île-de-France Region, France

Location

Travere Investigational Site

München, Bavaria, 80336, Germany

Location

Travere Investigational Site

Milan, Italy

Location

Travere Investigational Site

Oslo, Norway

Location

Travere Investigational Site

Warsaw, Poland

Location

Travere Investigational Site

Barcelona, Catalonia, 08035, Spain

Location

Travere Investigational Site

Barcelona, Spain

Location

Related Publications (1)

• Klopstock T, Escolar ML, Marshall RD, Perez-Duenas 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 primary efficacy outcome in patients with pantothenate kinase-associated neurodegeneration. Clin Trials. 2019 Aug;16(4):410-418. doi: 10.1177/1740774519845673. Epub 2019 May 6.

  PMID: 31055958 RESULT

MeSH Terms

Conditions

Pantothenate Kinase-Associated Neurodegeneration

Interventions

fosmetpantotenate

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

Limitations and Caveats

The study was terminated since fosmetpantotenate did not show statistically significant effects or clinical benefits during the double-blind period.

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: Retrophin, Inc.

medinfo@retrophin.com

+1-877-659-5518

Study Officials

• Thomas Klopstock, MD

  Klinikum der Universität München

  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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: February 2, 2017
• Study Start: July 17, 2017
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: January 26, 2021
• Results First Posted: December 29, 2020

Record last verified: 2021-01

Locations

US (9); ES (2); CA (2); DE (1); NO (1); IT (1); CZ (1); FR (2); PL (1)