Recruiting
Phase 1
Phase 2

S230815

Sponsor:

Institut de Recherches Internationales Servier

Code:

NCT07227857

Conditions

Epileptic Encephalopathy

Eligibility Criteria

Sex: All

Age: 2 - 12

Healthy Volunteers: Not accepted

Interventions

S230815- Starting dose A

S230815- Dose B

S230815- Dose C

S230815- Dose D

Study Details

Brief 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.

Conditions

Epileptic Encephalopathy

Study ID

NCT07227857

Start date

Nov 24, 2025

Status verified date

Aug, 2026

Completion date

Apr 15, 2028

Anticipated

Primary completion date

Apr 15, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 2 - 12

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

20 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1

experimental: Cohort 2

experimental: Cohort 3

experimental: Cohort 4

Interventions

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

Primary outcome measure

  • Incidence and severity of Adverse Events (AE)'s. [ Time Frame: Through End of study visit (A maximum of 116 weeks) ]

Central Contacts and Locations

Central contacts

Institut de Recherches Internationales Servier

+33 1 55 72 60-00scientificinformation@servier.com

Locations

Boston Children's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Christelle Achkar

Christelle.Achkar@childrens.harvard.edu

More Information

Sponsor

Institut de Recherches Internationales Servier

Last update posted

Aug 11, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Institut de Recherches Internationales Servier on 2026-08-11.