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

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 Pediatric Participants With KCNT1-related Developmental and Epileptic Encephalopathy

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.

Study Overview

• Status: Recruiting
• Conditions: Epileptic Encephalopathy
• Intervention / Treatment: Drug: S230815- Starting dose A; Drug: S230815- Dose B; Drug: S230815- Dose C; Drug: S230815- Dose D

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier; Phone Number: +33 1 55 72 60-00; Email: scientificinformation@servier.com

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • Institut Des Neurosciences De La Timone
    • Contact: Mathieu Milh, Pr; Phone Number: 0491388613; Email: Mathieu.MILH@ap-hm.fr
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker Enfants Malades
    • Contact: Rima Nabbout, Pr; Phone Number: 0144381536; Email: rima.nabbout@aphp.fr
  • Paris, France, 75019
    • Recruiting
    • Robert Debre University Hospital
    • Contact: Stephane AUVIN; Phone Number: 0140035724; Email: stephane.auvin@aphp.fr
• Italy
  • Florence, Italy, 50139
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria Meyer IRCCS
    • Contact: Renzo Guerrini, Pr; Phone Number: +390555662573; Email: renzo.guerrini@meyer.it
  • Roma, Italy, 00165
    • Not yet recruiting
    • Ospedale Pediatrico Bambino Gesu
    • Contact: Nicola Specchio, Pr; Phone Number: +390668592645; Email: nicola.specchio@opbg.net
• Japan
  • Nagano, Japan
    • Recruiting
    • Shinshu University Hospital
    • Contact: Tetsuhiro Fukuyama
  • Osaka, Japan
    • Recruiting
    • Osaka City General Hospital
    • Contact: Shin Okazaki
  • Shizuoka, Japan
    • Recruiting
    • Shizuoka Institute of Epilepsy and Neurological Disorders
    • Contact: Satoshi Mizutani
• Spain
  • Esplugues de Llobregat, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Deu Barcelona
    • Contact: Yana Dominguez, Dr; Phone Number: +34936009733; Email: jana.dominguez@sjd.es
  • Madrid, Spain, 28035
    • Recruiting
    • Hospital Ruber Internacional
    • Contact: Antonio Gil-Nagel Rein, Dr; Phone Number: +34913875250; Email: gilnagel.ensayos@neurologiaclinica.es
• United States
  • California
    • Orange, California, United States, 92868
      • Not yet recruiting
      • Children's Hospital of Orange County
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Christelle Achkar; Email: Christelle.Achkar@childrens.harvard.edu
  • New York
    • Rochester, New York, United States, 14642
      • Not yet recruiting
      • University of Rochester Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Not yet recruiting
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • The Children's Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75235
      • Not yet recruiting
      • Children's Health Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: S230815- Starting dose A; Solution for injection
Experimental: Cohort 2	Drug: S230815- Dose B; Solution for injection
Experimental: Cohort 3	Drug: S230815- Dose C; Solution for injection
Experimental: Cohort 4	Drug: S230815- Dose D; Solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of Adverse Events (AE)'s.	Through End of study visit (A maximum of 116 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameters of S230815 in cerebrospinal fluid (CSF) Ctrough	Ctrough is defined as the concentration reached immediately before the next dose is administered.	Through week 96
Pharmacokinetic (PK) parameters of S230815 in plasma AUC 0-τ	Area Under the Curve (AUC) from dosing (time 0) to time t [AUC0-t]	Through End of study visit (A maximum of 116 weeks)
Pharmacokinetic (PK) parameters of S230815 in plasma Cmax	Cmax is defined as the maximum (peak) observed concentration following a dose. Measured 0.5, 2, 4, 8 , and 24 hours post dose	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)
Relative change from baseline in seizure frequency as recorded by periodic 24h Video Electroencephalogram (vEEG) assessment		Through End of study visit (A maximum of 116 weeks)
Number and administration frequency of rescue medication		Through End of study visit (A maximum of 116 weeks)

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2025
• Primary Completion (Estimated): April 15, 2028
• Study Completion (Estimated): April 15, 2028

Study Registration Dates

• First Submitted: November 12, 2025
• First Submitted That Met QC Criteria: November 12, 2025
• First Posted (Actual): November 13, 2025

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: CL1-230815-001; 2024-513332-17-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No