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A Phase Ib/II first-in-human, multicentre, open-label, multiple ascending dose study of S230815 in paediatric participants with KCNT1-related Developmental and Epileptic Encephalopathy

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	KCNT1-related Developmental and Epileptic Encephalopathy
Date of first enrollment	01/04/2026
Target sample size	20
Countries of recruitment	United States,Japan,France,Japan,Italy,Japan,Spain,Japan
Study type	Interventional
Intervention(s)	Drug: S230815- Starting dose A to Maximum dose D for each cohort Solution for injection

Outcome(s)

Primary Outcome

- Incidence and severity of AEs.

Secondary Outcome

Pharmacokinetic parameters of S230815 in cerebrospinal fluid Ctrough Pharmacokinetic parameters of S230815 in plasma AUC Pharmacokinetic parameters of S230815 in plasma Cmax Pharmacokinetic parameters of S230815 in plasma Ctrough Relative change from baseline in seizure frequency as recorded by daily seizure logs Relative change from baseline in seizure frequency as recorded by periodic 24h Video Electroencephalogram (vEEG) assessment Number and administration frequency of rescue medication

Key inclusion & exclusion criteria

Age minimum	>= 2age old
Age maximum	<= 12age old
Gender	Both
Include criteria	- Male or female paediatric participants aged 2-12 years old at screening, with a genetically confirmed diagnosis of DEE (EIMFS or non-EIFMS EOEE phenotypes) 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).
Exclude criteria	- Other clinical phenotypes associated with pathogenic or likely pathogenic variants in KCNT1 other than EIMFS or EOEE (e.g., SHE). - 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 medical history or clinical findings on physical examination, other than DEE, that in the judgment of the investigator, make the participant unsuitable for participation in the study and/or completion of the trial procedures, including, but not limited to: - Clinically significant prior or ong/oing medical conditions within 30 days of the screening visit, as per investigator judgement. - Clinically significant abnormality on ECG at the screening visit, as per investigator judgement. - Clinically significant abnormality on laboratory testing at screening, including, but not limited to: - Renal insufficiency, which is defined as creatinine clearance less than 40 mL/min assessed as estimated Glomerular Filtration Rate (eGFR) using Schwartz formula - Hepatic derangement defined as transaminase values more than 3 times the Upper Limit of Normal (ULN) range or total bilirubin values more than 1.5 times the ULN - Positive hepatitis B surface antigen test, positive hepatitis C antibody test, positive for human immunodeficiency virus (HIV), as reported by a laboratory test within 6 months prior to the screening visit, or on screening bloods. - Bone, spine, bleeding disorders, or other disorder that exposes the participant to risk of injury or unsuccessful LP (e.g., haemophilia, Von Willebrand's disease, liver disease). - Contraindications to MRI, LP procedure and IT administration. - History of CNS tumors or malignancies, including CNS metastatic disease. - Continuous respiratory support, defined as oxygen supplementation or non-invasive ventilation (e.g.: continuous positive airway pressure, bi-level intermittent positive airway pressure), required during waking hours. This does not include suctioning; cough assist devices or other devices that may be used regularly to clear airwways. - Invasive ventilation including the presence of a tracheostomy. - Use of quinidine within 30 days prior to the screening visit. - Current use or anticipated use of antiplatelet or anticoagulant therapy during the study. - Current or past enrolment in an interventional clinical study in which an investigational therapy is/was administered within 30 days (or 5 half-lives of study agent, whichever is longer) prior to the screening visit. - Implantable CNS device that may interfere with the ability to administer the study drug via LP. - Known hypersensitivity to any oligonucleotide, as demonstrated by a systemic allergic reaction (e.g., changes in pulse, blood pressure, breathing function, etc...), or any other drug that in the opinion of the investigator may preclude study participation.