E.1 Medical condition or disease under investigation |
E.1.1 | 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. |
La neurodégénérescence associée à la pantothénate kinase (PKAN, pantothenate kinase associated neurodegeneration), est un trouble génétique récessif autosomique, la forme la plus fréquente de neurodégénérescence avec accumulation de fer dans le cerveau (NBIA, Neurodegeneration with Brain Iron Accumulation). C'est une maladie neurodégénérative
progressive, souvent fatale. |
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E.1.1.1 | Medical condition in easily understood language |
Neurodegenerative disease. |
Maladie neurodégénérative |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053643 |
E.1.2 | Term | Neurodegenerative disorder |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | 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. |
Évaluer l’efficacité du fosmetpantoténate pendant 24 semaines chez des patients présentant une neurodégénérescence associée à la pantothénate kinase-(PKAN).
Évaluer la tolérance et la sécurité du fosmetpantoténate chez les patients présentant une PKAN. |
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E.2.2 | 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. |
Déterminer la pharmacocinétique (PK) après des doses multiples de fosmetpantoténate chez les patients présentant une PKAN.
Explorer les biomarqueurs potentiels de la maladie, ainsi que leur réponse potentielle au traitement chez les patients présentant une PKAN |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The patient has a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 (PANK2) gene.
- The patient has a score of ≥ 6 on the Pantothenate Kinase-associated Neurodegeneration Activities of Daily Living (PKAN-ADL) scale. |
- Diagnostic de PKAN indiqué par des mutations confirmées du gène de la pantothénate kinase 2 (PANK2).
- Score de ≥ 6 sur l’échelle PKAN-ADL (neurodégénérescence associée à la pantothénate kinase-activités de la vie quotidienne). |
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E.4 | 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 for the double-blind period of the study.
- The patient has taken deferiprone within 30 days prior to screening. |
- Nécessité d’un soutien ventilatoire invasif intermittent ou régulier pour maintenir les signes vitaux dans les 24 semaines précédant la randomization.
- Implantation d’un dispositif de stimulation cérébrale profonde (DBS) dans les 6 mois précédant la selection.
- Incapacité ou refus du patient à maintenir pendant la période de l’étude en double insu les doses d’avant l’étude de médicaments et de traitements d’entretien concomitants autorisés pour la PKAN.
- Prise de défériprone dans les 30 jours précédant la sélection. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint
- Change in the score from the PKAN-ADL
Safety Endpoint
- Safety and tolerability |
Critère d’évaluation principal de l’efficacité
- Variation du score PKAN-ADL
Critères d’évaluation de la tolérance
- Sécurité et tolérance |
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E.5.1.1 | 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. |
Pour chaque patient, la variation du score PKAN-ADL observée aux Semaines 3, 6, 12, 18, et 24 de la période en double insu, par rapport à l’inclusion, sera utilisée pour l’analyse. |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoint
- Change in the score from Part III of the UPDRS |
Critères d’évaluation secondaires de l’efficacité
- Variation du score de la Partie III de l’échelle d’évaluation unifiée de la maladie de Parkinson (UPDRS) |
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E.5.2.1 | 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. |
Mesures continues enregistrées à chaque visite d'étude entre l’inclusion et la fin de la période de 24 semaines en double insu.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Czech Republic |
France |
Germany |
Italy |
Norway |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
Dernière visite du dernier patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |