A Phase Ib/II first-in-human, multicentre, open-label, multiple ascending dose study of S230815 in paediatric participants with KCNT1-related Developmental and Epileptic Encephalopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 Nov 2025 → ongoing

Decision date (initial)

2025-08-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ADIR France · Laboratorios Servier, S. L

External identifiers

EU CT number

2024-513332-17-00

ClinicalTrials.gov

NCT07227857

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety, Dose response, Others

To evaluate the safety and tolerability of S230815 in paediatric participants with KCNT1-Developmental and Epileptic Encephalopathy (KCNT1-DEE).

Secondary objectives 2

1. To characterize the pharmacokinetics (PK) of S230815 [commercially confidential information (CCI)].
2. To evaluate the clinical effect of S230815 on seizure activity.

Conditions and MedDRA coding

KCNT1-related Developmental and Epileptic Encephalopathy

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Food And Drug Administration, National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

Yes

IPD plan description

Servier’s Data Sharing Policy is available at https://clinicaltrials.servier.com/data-request-portal/. Researchers can ask for a study protocol, patient-level and/or study-level clinical study data including clinical study reports. They can ask for all interventional clinical studies in patients: Submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area(EEA) or the United States(US). Where Servier or an affiliate are the Marketing Authorisation Holders(MAH). The date of the first Marketing Authorisation(MA) of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope. In addition, Servier’s data sharing policy includes all interventional clinical studies in patients: sponsored by Servier, with a first patient enrolled as of 1 January 2004 onwards, for New Chemical or Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any MA approval.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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]
2. [CCI] Seizure count data will be captured by daily family seizure logs.
3. [CCI] stable dose of other regular medications and/or stable antiseizure interventions (such as ketogenic diet and vagal nerve stimulation).[CCI]
4. Must meet age-appropriate institutional guidelines for LP procedure.

Exclusion criteria 14

1. Other clinical phenotypes associated with pathogenic or likely pathogenic variants in KCNT1 other than EIMFS or EOEE (e.g., Sleep-related Hypermotor Epilepsy SHE).
2. Use of quinidine within 30 days prior to the screening visit.
3. Current use or anticipated use of antiplatelet or anticoagulant therapy during the study.
4. 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.
5. Implantable CNS device that may interfere with the ability to administer the study drug via LP.
6. 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.
7. 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.
8. 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.
9. 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).
10. Contraindications to undergoing Magnetic Resonance Imaging (MRI), lumbar puncture (LP) procedure and intrathecal (IT) administration.
11. History of Central Nervous System (CNS) tumors or malignancies, including CNS metastatic disease.
12. 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.
13. Invasive ventilation including the presence of a tracheostomy.
14. History of hydrocephalus requiring a ventriculoperitoneal shunt

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and severity of adverse events (AEs).

Secondary endpoints 1

1. PK parameters of S230815 [CCI] Cmax, plasma Ctrough and plasma AUC0-τ [CCI]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 13

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 105 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications