Ireland
--:--IST
Latest
Clinical Trials in Italy / NCT07227857
Recruiting Phase 1/2

A First-in-human Study of S230815 in Pediatric Participants With KCNT1-related Developmental and Epileptic Encephalopathy

NCT07227857 · tracked via the Priya Life Science Italy tracker
Phase
Phase 1/2
Started
2025-11-24
Last updated
2026-08-11

Condition(s) studied

Epileptic Encephalopathy

Investigational drug(s) / intervention(s)

S230815- Starting dose AS230815- Dose BS230815- Dose CS230815- Dose D

S230815- Starting dose A: Solution for injection

S230815- Dose B: Solution for injection

S230815- Dose C: Solution for injection

S230815- Dose D: Solution for injection

Study summary

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.

Eligibility

Sex
ALL
Min age
2 Years
Max age
12 Years
Healthy volunteers
No
Inclusion Criteria: * 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). Exclusion Criteria: * 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 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 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. * Clinically significant abnormality on laboratory testing at screening, including, but not limited to: * Renal insufficiency, which is defined as creatinine clearance \< 40 mL/min assessed as estimated glomerular filtration rate (eGFR) using Modification of Diet in Renal Disease (MDRD) 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 Lumbar puncture (e.g., haemophilia, Von Willebrand's disease, liver disease). * Contraindications to undergoing Magnetic Resonance Imaging (MRI), Lumbar puncture procedure and Intrathecal administration. * History of Central Nervous System (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 airways. * 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 Lumbar puncture. * 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. * History of hydrocephalus requiring a ventriculoperitoneal shunt.

Primary outcome measure(s)

Trial sites (15)

FacilityCityRegionStatus
Children's Hospital of Orange County Orange California Not Yet Recruiting
Boston Children's Hospital Boston Massachusetts Recruiting
University of Rochester Medical Center Rochester New York Not Yet Recruiting
Nationwide Children's Hospital Columbus Ohio Not Yet Recruiting
The Children's Hospital of Philadelphia Philadelphia Pennsylvania Not Yet Recruiting
Institut Des Neurosciences De La Timone Marseille France Recruiting
Hopital Necker Enfants Malades Paris France Recruiting
Robert Debre University Hospital Paris France Recruiting
Azienda Ospedaliera Universitaria Meyer IRCCS Florence Italy Not Yet Recruiting
Ospedale Pediatrico Bambino Gesu Roma Italy Not Yet Recruiting
Shinshu University Hospital Nagano Japan Recruiting
Osaka City General Hospital Osaka Japan Recruiting
Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka Japan Recruiting
Hospital Sant Joan De Deu Barcelona Esplugues de Llobregat Spain Recruiting
Hospital Ruber Internacional Madrid Spain Recruiting

More Institut de Recherches Internationales Servier trials in Italy

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07227857 on ClinicalTrials.gov ↗ ← All trials in Italy