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

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

Official Title
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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

Conditions
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Pantothenate Kinase-Associated Neurodegeneration

Intervention / Treatment
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* Drug: Fosmetpantotenate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosmetpantotenate<br>Administered as powder for reconstitution. | Drug: Fosmetpantotenate<br>* Daily dosing<br>* Other names: RE-024;|
| Placebo Comparator: Placebo<br>Administered as powder for reconstitution. | Drug: Placebo<br>* Daily dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PKAN