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A Phase Ib/II first-in-human, multicentre, open-label, multiple ascending dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effect of intrathecal S230815 in paediatric participants with KCNT1-related Developmental and Epileptic Encephalopathy (A first-in-human study of S230815 in paediatric participants with KCNT1-related Developmental and Epileptic Encephalopathy)

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 (KANDLE)

ROMERO Elodie

Institut de Recherches Internationales Servier (I.R.I.S.)

22 route 128 / rue Francis Perrin 91190 Gif-sur-Yvette, FRANCE

kandle-medical-team@servier.com

ICTR-Japan

Nihon Servier Company Limited

Otemachi Financial City Grand Cube, 1-9-2 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan

+81-3-4520-2344

clinicaltrials.jpn@servier.com

Recruiting

April. 01, 2026

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- 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).

- 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.

Both

KCNT1-related Developmental and Epileptic Encephalopathy

Drug: S230815- Starting dose A to Maximum dose D for each cohort
Solution for injection

KCNT1

- Incidence and severity of AEs.

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

+81-6-6929-3269

Feb. 24, 2026

+81-263-35-4600

Feb. 24, 2026

+81-54-245-5446

Feb. 24, 2026

No

United States/France/Italy/Spain