|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive genetic disorder, the most common form of Neurodegeneration with Brain Iron Accumulation (NBIA). It is a progressive, often fatal, neurodegenerative disease.
|Medical condition in easily understood language
|Diseases [C] - Nervous System Diseases [C10]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10029205 - Nervous system disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The efficacy objective of this study is to evaluate the efficacy of fosmetpantotenate over 24 weeks in patients with PKAN.
The safety objective of the study is to assess the safety and tolerability of fosmetpantotenate in patients with PKAN.
|Secondary objectives of the trial
|To determine the PK following multiple doses of fosmetpantotenate in patients with PKAN.
To explore potential biomarkers of disease, along with their potential response to treatment in patients with PKAN.
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|Additional Exploratory Assessment for Research
A blood sample will be collected at 2-3 different investigational sites from up to a total of 8 eligible patients (half adult, half pediatric) with different confirmed mutations in PANK2 to generate peripheral blood mononuclear cells (PBMCs).
To be eligible to participate, patients must have negative serologic tests for all tests outlined in Section 15.2.2 in the Clinical Trial Protocol. Patients will be required to sign a separate consent to participate in this exploratory sub-study. If a patient discontinues participation in the sub-study, their participation in the main study will not be affected.
|Principal inclusion criteria
|- The patient has a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 (PANK2) gene (if available, the specific mutation will be recorded).
- The patient has a score of ≥ 6 on the Pantothenate Kinase-associated Neurodegeneration Activities of Daily Living (PKAN-ADL) scale.
|Principal exclusion criteria
|- The patient has required regular or intermittent invasive ventilatory support to maintain vital signs within 24 weeks prior to randomization.
- The patient has had a deep brain stimulation (DBS) device implanted within 6 months prior to screening.
- The patient is unable or unwilling to remain on their pre-study dose(s) of allowed concomitant PKAN maintenance medications and therapies (including DBS settings) for the double-blind period of the study.
- The patient has taken deferiprone within 30 days prior to screening.
|E.5 End points
|Primary end point(s)
|Primary Efficacy Endpoint
- Change in the score from the PKAN-ADL, from Baseline to the end of the 24-week double-blind period
- Safety and tolerability of fosmetpantotenate
|Timepoint(s) of evaluation of this end point
|For each patient, the change from Baseline in PKAN-ADL scores at Weeks 3, 6, 12, 18, and 24 of the double-blind period will be used for analysis.
|Secondary end point(s)
|Secondary Efficacy Endpoint
- Change in the score from Part III of the Unified Parkinson’s Disease Rating Scale (UPDRS) from Baseline to the end of the 24-week double-blind period
|Timepoint(s) of evaluation of this end point
|Continuous measures recorded at each study visit from Baseline to the end of the 24-week double-blind period.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days