S230815-2 for KCNT1-related developmental and epileptic encephalopathy

Inclusion criteria

• {"criterion_text":"- Male or female paediatric participants aged 2-12 years old at screening, with a genetically confirmed diagnosis of Developmental Epileptic Encephalopathy (DEE) (Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) or non-EIFMS Early-Onset Epileptic Encephalopathy (EOEE) phenotypes) due to a pathogenic or likely pathogenic variant in KCNT1 confirmed by central genetic testing.[CCI]"}
• {"criterion_text":"- [CCI] Seizure count data will be captured by daily family seizure logs."}
• {"criterion_text":"- [CCI] stable dose of other regular medications and/or stable antiseizure interventions (such as ketogenic diet and vagal nerve stimulation).[CCI]"}
• {"criterion_text":"- Must meet age-appropriate institutional guidelines for LP procedure."}

Exclusion criteria

• {"criterion_text":"- Other clinical phenotypes associated with pathogenic or likely pathogenic variants in KCNT1 other than EIMFS or EOEE (e.g., Sleep-related Hypermotor Epilepsy SHE)."}
• {"criterion_text":"- Contraindications to undergoing Magnetic Resonance Imaging (MRI), lumbar puncture (LP) procedure and intrathecal (IT) administration."}
• {"criterion_text":"- History of Central Nervous System (CNS) tumors or malignancies, including CNS metastatic disease."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Invasive ventilation including the presence of a tracheostomy."}
• {"criterion_text":"- History of hydrocephalus requiring a ventriculoperitoneal shunt"}
• {"criterion_text":"- Use of quinidine within 30 days prior to the screening visit."}
• {"criterion_text":"- Current use or anticipated use of antiplatelet or anticoagulant therapy during the study."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Implantable CNS device that may interfere with the ability to administer the study drug via LP."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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: 1) Clinically significant prior or ongoing medical conditions within 30 days of the screening visit, as per investigator judgement. 2) Clinically significant abnormality on electrocardiogram (ECG) at the screening visit, as per investigator judgement. 3) Clinically significant abnormality on laboratory testing at screening, including, but not limited to: a) Renal insufficiency, which is defined as creatinine clearance < 40 mL/min assessed as estimated glomerular filtration rate (eGFR) using Schwartz formula, b) 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}

Primary endpoints

• {"endpoint_text":"- Incidence and severity of adverse events (AEs).","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- PK parameters of S230815 [CCI] Cmax, plasma Ctrough and plasma AUC0-τ [CCI]","definition_or_measurement_approach":"Plasma pharmacokinetic parameters: Cmax, plasma Ctrough and plasma AUC0-τ (as stated)."}

Methods

• Recruitment materials and advertisements (document titles: 'L2_Recruitment Material_Advertisement_FRA_fr', 'K1_Recruitment arrangement_Advertisement' and country-specific K2 recruitment materials) — country-targeted advertisements and recruitment brochures referenced in submitted recruitment documents.
• Caregiver and parent brochures and information materials (document titles: 'K1_Recruitment arrangement_Caregiver_brochure', 'K2_Caregiver study brochure_ITA_it') aimed at caregivers/parents.
• Patient introduction and information videos (document titles: 'K1_Recruitment arrangement_Patient_video_script_ESP', 'L2_Patient introduction video and information video transcripts_FRA_fr', and country-specific video transcripts) used to inform potential participants and families.
• Use of electronic patient-facing eDiary/eCOA and digital health technology in study conduct (e.g., 'D4_Patient facing documents_eDiary_EN_FP' and vendor Signant Health and Empatica involvement) which may be used for patient-reported data capture and remote monitoring.

France

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

234

Number Of Sites

3

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

05-08-2025

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

220

Number Of Sites

2

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

08-10-2025

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

197

Number Of Sites

2

Number Of Participants

8

Primary sponsor

Full Name

Institut De Recherches Internationales Servier IRIS

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

IQVIA Limited

Responsibilities

Study monitoring

Name

Biotrial

Responsibilities

Safety central reading (ECG, EEG, MRI)

Third parties

• {"country":"United States","full_name":"Ncs Pearson Inc.","duties_or_roles":"Neurodevelopment Questionnaire","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Signant Health Global Solutions Limited","duties_or_roles":"e-lectronic Clinical Outcome Assessment (eCOA)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long term samples storage","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"SGS France","duties_or_roles":"PK and ADA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Active Biomarkers","duties_or_roles":"Biomarker analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Empatica Inc.","duties_or_roles":"Digital Health Technology, Wearable","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"BiognoSYS AG","duties_or_roles":"Biomarker analysis","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Firalis","duties_or_roles":"Biomarker analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Study monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Biotrial","duties_or_roles":"Safety central reading (ECG, EEG, MRI)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Genetic testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"C.D.L. Pharma S.A.S.","duties_or_roles":"Logistic Platform","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clouds of Care","duties_or_roles":"Exploratory central reading (EEG)","organisation_type":"Pharmaceutical company"}