Study CL1-230815-001 (KANDLE) is a Phase Ib/II, First In Human, multicentre, open-label, multiple ascending dose study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effect of S230815 in pediatric participants with KCNT1-related Developmental Epileptic Encephalopathy. To participate in the study, participants must have a diagnosis of Developmental Epileptic Encephalopathy due to a documented pathogenic or likely pathogenic variant in KCNT1 (to be confirmed by central genetic testing at the screening visit). The study consists of a screening period followed by two consecutive interventional parts. Part 1 will evaluate multiple ascending doses of S230815. Part 2 is a long-term treatment extension for participants who have completed Part 1. Participants will seamlessly roll-over from Part 1 to Part 2, resuming the same cohort as they were assigned in Part 1, and will receive S230815 for a maximum of 72 weeks.
Male or female pediatric participants aged 2-12 years old at screening, with a genetically confirmed diagnosis of Developmental Epileptic Encephalopathy (DEE) due to a pathogenic or likely pathogenic variant in KCNT1 confirmed by central genetic testing.
Stable dose of other regular medications and/or stable antiseizure interventions (such as ketogenic diet and vagal nerve stimulation).
Other clinical phenotypes associated with pathogenic or likely pathogenic variants in KCNT1 other than Epilepsy of Infancy with Migrating Focal Seizures or Early-Onset Epileptic Encephalopathy
Documented pathogenic or likely pathogenic variants in any other gene known to cause epilepsy identified through prior genetic testing. Variants of uncertain significance in other genes known to cause epilepsy may be considered on discussion with the sponsor.
Clinically significant prior or ongoing medical conditions within 30 days of the screening visit, as per investigator judgement.
Clinically significant abnormality on Electrocardiogram (ECG) at the screening visit, as per investigator judgement.
Sequential
S230815- Starting dose A
DrugSolution for injection
S230815- Dose B
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S230815- Dose C
DrugSolution for injection
S230815- Dose D
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Incidence and severity of Adverse Events (AE)'s.
Pharmacokinetic (PK) parameters of S230815 in cerebrospinal fluid (CSF) Ctrough
Ctrough is defined as the concentration reached immediately before the next dose is administered.
Pharmacokinetic (PK) parameters of S230815 in plasma AUC 0-τ
Area Under the Curve (AUC) from dosing (time 0) to time t \[AUC0-t\]
Pharmacokinetic (PK) parameters of S230815 in plasma Cmax
Cmax is defined as the maximum (peak) observed concentration following a dose. Measured 0.5, 2, 4, 8 , and 24 hours post dose
Pharmacokinetic (PK) parameters of S230815 in plasma Ctrough
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