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

NCT07227857 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CL1-230815-0012024-513332-17-00
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 16

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

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of Adverse Events (AE)'s.

  Through End of study visit (A maximum of 116 weeks)

Secondary Outcomes (7)

• Pharmacokinetic (PK) parameters of S230815 in cerebrospinal fluid (CSF) Ctrough

  Through week 96

• Pharmacokinetic (PK) parameters of S230815 in plasma AUC 0-τ

  Through End of study visit (A maximum of 116 weeks)

• Pharmacokinetic (PK) parameters of S230815 in plasma Cmax

  Through End of study visit (A maximum of 116 weeks)

• Pharmacokinetic (PK) parameters of S230815 in plasma Ctrough

  Through End of study visit (A maximum of 116 weeks)

• Relative change from baseline in seizure frequency as recorded by daily seizure logs

  Through End of study visit (A maximum of 116 weeks)

Study Arms (4)

Cohort 1

EXPERIMENTAL

Drug: S230815- Starting dose A

Cohort 2

EXPERIMENTAL

Drug: S230815- Dose B

Cohort 3

EXPERIMENTAL

Drug: S230815- Dose C

Cohort 4

EXPERIMENTAL

Drug: S230815- Dose D

Interventions

S230815- Dose B DRUG

Solution for injection

Cohort 2

S230815- Dose C DRUG

Solution for injection

Cohort 3

S230815- Dose D DRUG

Solution for injection

Cohort 4

S230815- Starting dose A DRUG

Solution for injection

Cohort 1

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead

Study Sites (16)

Children's Hospital of Orange County

Orange, California, 92868, United States

NOT YET RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

NOT YET RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

NOT YET RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Children's Health Dallas

Dallas, Texas, 75235, United States

NOT YET RECRUITING

Institut Des Neurosciences De La Timone

Marseille, 13005, France

RECRUITING

Hopital Necker Enfants Malades

Paris, 75015, France

RECRUITING

Robert Debre University Hospital

Paris, 75019, France

RECRUITING

Azienda Ospedaliera Universitaria Meyer IRCCS

Florence, 50139, Italy

NOT YET RECRUITING

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

NOT YET RECRUITING

Shinshu University Hospital

Nagano, Japan

NOT YET RECRUITING

Osaka City General Hospital

Osaka, Japan

NOT YET RECRUITING

Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Japan

NOT YET RECRUITING

Hospital Sant Joan De Deu Barcelona

Esplugues de Llobregat, 08950, Spain

RECRUITING

Hospital Ruber Internacional

Madrid, 28035, Spain

RECRUITING

Central Study Contacts

Institut de Recherches Internationales Servier

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2025
• First Posted: November 13, 2025
• Study Start: November 24, 2025
• Primary Completion (Estimated): April 15, 2028
• Study Completion (Estimated): April 15, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

FR (3); IT (2); US (6); ES (2); JP (3)