Epileptic EncephalopathyPhase 1/2KANDLENCT07227857
A First-in-human Study of S230815 in Pediatric Participants With KCNT1-related Developmental and Epileptic Encephalopathy
A Phase 1/2 study testing S230815- Starting dose A, S230815- Dose B and S230815- Dose C in people with Epileptic Encephalopathy, run by Institut de Recherches Internationales Servier at 15 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Epileptic Encephalopathy
- What is being tested?
- S230815- Starting dose A, S230815- Dose B and S230815- Dose C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 24 Nov 2025to 15 Apr 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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:
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- 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.
Trial locations and contacts
15 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
Institut de Recherches Internationales Servier contact
15 sites in 5 countries
United States5 sites, 5 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Christelle Achkar, Christelle.Achkar@childrens.harvard.edu
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
- Not yet recruiting
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
- Not yet recruiting
University of Rochester Medical Center
Rochester, New York, 14642
France3 sites, 3 recruiting
- Recruiting
Institut Des Neurosciences De La Timone
Marseille, 13005
Mathieu Milh, Pr, 0491388613, Mathieu.MILH@ap-hm.fr
- Recruiting
Hopital Necker Enfants Malades
Paris, 75015
Rima Nabbout, Pr, 0144381536, rima.nabbout@aphp.fr
- Recruiting
Robert Debre University Hospital
Paris, 75019
Stephane AUVIN, 0140035724, stephane.auvin@aphp.fr
Japan3 sites, 3 recruiting
- Recruiting
Shinshu University Hospital
Nagano
Tetsuhiro Fukuyama
- Recruiting
Osaka City General Hospital
Osaka
Shin Okazaki
- Recruiting
Shizuoka Institute of Epilepsy and Neurological Disorders
Shizuoka
Satoshi Mizutani
Italy2 sites, 2 recruiting
- Not yet recruiting
Azienda Ospedaliera Universitaria Meyer IRCCS
Florence, 50139
Renzo Guerrini, Pr, +390555662573, renzo.guerrini@meyer.it
- Not yet recruiting
Ospedale Pediatrico Bambino Gesu
Roma, 00165
Nicola Specchio, Pr, +390668592645, nicola.specchio@opbg.net
Spain2 sites, 2 recruiting
- Recruiting
Hospital Sant Joan De Deu Barcelona
Esplugues de Llobregat, 08950
Yana Dominguez, Dr, +34936009733, jana.dominguez@sjd.es
- Recruiting
Hospital Ruber Internacional
Madrid, 28035
Antonio Gil-Nagel Rein, Dr, +34913875250, gilnagel.ensayos@neurologiaclinica.es
About this study
Official title: 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.
- Conditions
- Epileptic Encephalopathy
- Being tested
- S230815- Starting dose A, S230815- Dose B, S230815- Dose C, S230815- Dose D
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S230815- Starting dose ADrug
Solution for injection
S230815- Dose BDrug
Solution for injection
S230815- Dose CDrug
Solution for injection
S230815- Dose DDrug
Solution for injection
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Not described Receives: Drug: S230815- Starting dose A |
| Cohort 2 | Experimental | Not described Receives: Drug: S230815- Dose B |
| Cohort 3 | Experimental | Not described Receives: Drug: S230815- Dose C |
| Cohort 4 | Experimental | Not described Receives: Drug: S230815- Dose D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of Adverse Events (AE)'s.
Measured: Through End of study visit (A maximum of 116 weeks)
Secondary outcomes (7)
Pharmacokinetic (PK) parameters of S230815 in cerebrospinal fluid (CSF) Ctrough
Ctrough is defined as the concentration reached immediately before the next dose is administered.
Measured: 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]
Measured: 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
Measured: Through End of study visit (A maximum of 116 weeks)
Pharmacokinetic (PK) parameters of S230815 in plasma Ctrough
Measured: Through End of study visit (A maximum of 116 weeks)
Relative change from baseline in seizure frequency as recorded by daily seizure logs
Measured: 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
Measured: Through End of study visit (A maximum of 116 weeks)
Number and administration frequency of rescue medication
Measured: Through End of study visit (A maximum of 116 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2025
- Study start24 Nov 2025
- Primary completion15 Apr 2028 (estimated)
- Study completion15 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epileptic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07227857
- Sponsor's protocol ID
- CL1-230815-001
- Other IDs
- 2024-513332-17-00
- Acronym
- KANDLE
- Status last verified
- Oct 2026
- First submitted
- 12 Nov 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07227857
- Acronym / sponsor ID
- KANDLE / CL1-230815-001
- Conditions
- Epileptic Encephalopathy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Study start
- 24 Nov 2025 (actual)
- Primary completion
- 15 Apr 2028 (estimated)
- Study completion
- 15 Apr 2028 (estimated)
- First posted
- 13 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (20 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S230815- Starting dose ASolution for injection | Drug | Cohort 1 |
| S230815- Dose BSolution for injection | Drug | Cohort 2 |
| S230815- Dose CSolution for injection | Drug | Cohort 3 |
| S230815- Dose DSolution for injection | Drug | Cohort 4 |
Primary outcome
Incidence and severity of Adverse Events (AE)'s.
Time frame: Through End of study visit (A maximum of 116 weeks)
7 secondary outcomes
Pharmacokinetic (PK) parameters of S230815 in cerebrospinal fluid (CSF) Ctrough
Time frame: Through week 96
Pharmacokinetic (PK) parameters of S230815 in plasma AUC 0-τ
Time frame: Through End of study visit (A maximum of 116 weeks)
Pharmacokinetic (PK) parameters of S230815 in plasma Cmax
Time frame: Through End of study visit (A maximum of 116 weeks)
Pharmacokinetic (PK) parameters of S230815 in plasma Ctrough
Time frame: Through End of study visit (A maximum of 116 weeks)
Relative change from baseline in seizure frequency as recorded by daily seizure logs
Time frame: 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
Time frame: Through End of study visit (A maximum of 116 weeks)
Number and administration frequency of rescue medication
Time frame: Through End of study visit (A maximum of 116 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Institut de Recherches Internationales Servier contact
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing S230815- Starting dose A, S230815- Dose B and S230815- Dose C in people with Epileptic Encephalopathy, run by Institut de Recherches Internationales Servier at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, France, Japan, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Institut de Recherches Internationales Servier (+33 1 55 72 60-00, scientificinformation@servier.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of Adverse Events (AE)'s. (time frame: Through End of study visit (A maximum of 116 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.