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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Solution for injection
Solution for injection
Solution for injection
Solution for injection
Children's Hospital of Orange County
Orange, California, United States
NOT_YET_RECRUITINGBoston Children's Hospital
Boston, Massachusetts, United States
NOT_YET_RECRUITINGUniversity of Rochester Medical Center
Rochester, New York, United States
NOT_YET_RECRUITINGNationwide Children's Hospital
Columbus, Ohio, United States
NOT_YET_RECRUITINGThe Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
NOT_YET_RECRUITINGChildren's Health Dallas
Dallas, Texas, United States
NOT_YET_RECRUITINGInstitut Des Neurosciences De La Timone
Marseille, France
RECRUITINGHopital Necker Enfants Malades
Paris, France
RECRUITINGRobert Debre University Hospital
Paris, France
RECRUITINGAzienda Ospedaliera Universitaria Meyer IRCCS
Florence, Italy
NOT_YET_RECRUITING...and 6 more locations
Incidence and severity of Adverse Events (AE)'s.
Time frame: Through End of study visit (A maximum of 116 weeks)
Pharmacokinetic (PK) parameters of S230815 in cerebrospinal fluid (CSF) Ctrough
Ctrough is defined as the concentration reached immediately before the next dose is administered.
Time frame: Through week 96
Pharmacokinetic (PK) parameters of S230815 in plasma AUC 0-τ
Area Under the Curve (AUC) from dosing (time 0) to time t \[AUC0-t\]
Time frame: Through End of study visit (A maximum of 116 weeks)
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
Time frame: Through End of study visit (A maximum of 116 weeks)
Pharmacokinetic (PK) parameters of S230815 in plasma Ctrough
Time frame: Through End of study visit (A maximum of 116 weeks)
Relative change from baseline in seizure frequency as recorded by daily seizure logs
Time frame: Through End of study visit (A maximum of 116 weeks)
Relative change from baseline in seizure frequency as recorded by periodic 24h Video Electroencephalogram (vEEG) assessment
Time frame: Through End of study visit (A maximum of 116 weeks)
Number and administration frequency of rescue medication
Time frame: Through End of study visit (A maximum of 116 weeks)
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