Investigate Efficacy and Safety of Carisbamate As Adjunctive Treatment for Seizures Associated with LGS in Children and Adults

Phase 3

Recruiting

• Conditions: Lennox Gastaut Syndrome; Seizures
• Interventions: Drug: Carisbamate

• Registration Number: NCT05219617
• Lead Sponsor: SK Life Science, Inc.

Brief Summary

The primary objective is to evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the number of drop seizures (tonic, atonic, and tonic-clonic) compared with placebo in pediatric and adult subjects (age 4-55 years) diagnosed with Lennox Gastaut Syndrome (LGS).

Detailed Description

The secondary objectives are:

* To evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the total number of seizures compared with placebo in pediatric and adult subjects diagnosed with Lennox Gastaut Syndrome (LGS)

* Evaluate the safety, tolerability of carisbamate in the LGS population

* Evaluate steady-state pharmacokinetics of carisbamate in subjects with Lennox Gastaut.

Study Timeline

• Study First Submitted: 2022-01-06
• Study First Submitted QC: 2022-01-20
• Study First Posted: 2022-02-02
• Study Start: 2022-04-28
• Status Verified: 2024-05
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-24
• Primary Completion: 2025-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 252

Inclusion Criteria

1. Subject must have a documented history of Lennox-Gastaut syndrome by:

   1. Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure
   2. History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern <3.0 Hz)
   3. History of developmental delay

2. Male or female subjects

3. Subjects must be age 4-55 years at the time of consent/assent

4. Must have been <11 years old at the onset of LGS

5. Subjects must have experienced at least 2 drop seizures with potential to fall (tonic, atonic, tonic-clonic) during the 4-week Baseline period preceding randomization (minimum of 4 drop seizures in the first two weeks and 4 in the last two weeks). Drop seizures are defined as a seizure involving the entire body, trunk, or head that led or could have led to a fall, injury, slumping in a chair, or hitting the subject's head on a surface. All drop seizure types must be countable (either as isolated seizures or as countable isolated seizures in a cluster).

6. Subjects must have been receiving 1 to 4 concomitant anti-seizure medications (ASMs) at a stable dose for at least 4 weeks before Visit 1

7. If not taking Epidiolex, subjects may take other approved cannabidiol or over the counter cannabidiol products. If taking cannabidiol other than Epidiolex, consult Medical Monitor to determine if it counts as a concomitant ASM.

8. Dietary therapy and any CNS stimulator settings must be stable for 4 weeks prior to baseline and maintain stable regimen throughout the study. The dietary therapy and CNS stimulators are not counted as an ASM.

9. Parents or caregivers must be able to keep accurate seizure diaries

10. Subject is either not of childbearing potential, defined as premenarchal, postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), if of childbearing potential, must comply with an acceptable method of birth control during the study, for at least 4 weeks prior to study entry and for 4 weeks following completion of the study, if able.

11. Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study

12. Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements

13. History of COVID-19 vaccination is permitted

Exclusion Criteria

1. Etiology of subject's seizures is a progressive neurologic disease. Subjects with tuberous sclerosis will not be excluded from study participation, unless there is a progressive brain tumor
2. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the subject's safety or study conduct
3. Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline
4. Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling
5. Current use of felbamate with less than 18 months of continuous exposure
6. Concomitant use of vigabatrin: subjects who took vigabatrin in the past must be discontinued for at least 5 months before Visit 1 and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test, if able.
7. Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline
8. Status epilepticus within 12 weeks prior to Visit 1
9. Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator
10. Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2)
11. Subject has a history of any serious drug-induced hypersensitivity, e.g., toxic epidermal necrolysis, or Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]) or any drug-related rash requiring hospitalization
12. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS) or other neurostimulation for epilepsy device implanted or activated <5 months year prior to enrollment. Stimulation parameters that have been stable for <4 weeks, or Battery life of unit not anticipated to extend for duration of trial.
13. Subject is pregnant, may be pregnant, lactating or planning to be pregnant
14. Any suicidal ideation with intent, with or without a plan within 6 months before Visit 2 (i.e., answering "Yes" to questions 4 or 5 in the Suicidal Ideation section of the age- specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated
15. Any suicidal behavior within 2 years before Visit 2 (i.e., answering YES to any question in the Suicidal behavior section of the age-specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated.
16. Evidence of significant active hepatic disease. Stable elevations of liver enzymes (alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) due to concomitant medication(s) will be allowed if they are <3 x ULN
17. Subject with total bilirubin [TBL] >2 x ULN (except for Gilbert's syndrome).
18. Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1)
19. History of positive antibody/antigen test for human immunodeficiency virus (HIV)
20. If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products
21. Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study
22. Subject who has taken or used any investigational drug or device in the 4 weeks prior to the screening visit (Visit 1)
23. Concomitant use of medications known to be strong inducers of cytochrome P450 (CYP3A) including, but not limited to: phenobarbital, phenytoin, carbamazepine, primidone, rifampin, troglitazone, St. John's Wort, efavirenz, nevirapine, glucocorticoids (other than topical usage), modafinil, pioglitazone, and rifabutin
24. Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome
25. Subject with a short QTc interval (<340 msec) or long QTc interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG)
26. Benzodiazepine rescue administered on average more than once a week in the month before Visit 1
27. Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carisbamate 200 mg BID arm	Carisbamate	Age: 4 to \<12y\* Titration: 2 mg/kg BID Maintenance: 4 mg/kg BID Age: ≥12 y Titration: 100 mg BID Maintenance: 200 mg BID
Carisbamate 300 mg BID arm	Carisbamate	Age: 4 to \<12y\* Titration: 2.75 mg/kg BID Maintenance: 5.5 mg/kg BID Age: ≥12 y Titration: 150 mg BID Maintenance: 300 mg BID
Placebo matched to 200 mg BID arm	Carisbamate	Age: 4 to \<12y\* Titration: Volume equivalent to 2 mg/kg BID Maintenance: Volume equivalent to 4 mg/kg BID Age: ≥12 y Titration: Volume equivalent to 100 mg BID Maintenance: Volume equivalent to 200 mg BID
Placebo matched to 300 mg BID arm	Carisbamate	Age: 4 to \<12y\* Titration: Volume equivalent to 2.75 mg/kg BID Maintenance: Volume equivalent to 5.5 mg/kg BID Age: ≥12 y Titration: Volume equivalent to 150 mg BID Maintenance: Volume equivalent to 300 mg BID

Primary Outcome Measures

Name	Time	Method
Primary outcome will be the percentage change from baseline in the total frequency (average per 28 days) of countable drop seizures with potential to fall (tonic, atonic, tonic-clonic) seizures during the double-blind treatment period.	3 years	Efficacy of Carisbamate YKP509

Secondary Outcome Measures

Name	Time	Method
Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period.	3 years	Efficacy of Carisbamate YKP509
The percentage of subjects with at least a 50% reduction from baseline in the total frequency of drop seizures (tonic, atonic, tonic-clonic) during the double-blind treatment period.	3 years	Efficacy of Carisbamate YKP509
Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit.	3 years	Efficacy of Carisbamate YKP509- Scoring will be from 1 to 7 with 1 (very much improved) to 7 (very much worse)

Trial Locations

Locations (71)

Stanford University Hospital; 🇺🇸 Palo Alto, California, United States

University of Florida Health Science Center; 🇺🇸 Jacksonville, Florida, United States

AdventHealth; 🇺🇸 Orlando, Florida, United States

Pediatric Epilepsy and Neurology Specialists; 🇺🇸 Tampa, Florida, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Axcess Medical Research; 🇺🇸 Wellington, Florida, United States

Consultants in Epilepsy and Neurology PLLC; 🇺🇸 Boise, Idaho, United States

Bluegrass Epilepsy Research, LLC; 🇺🇸 Lexington, Kentucky, United States

University Medical Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Mid-Atlantic Epilepsy and Sleep Center; 🇺🇸 Bethesda, Maryland, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Missouri School of Medicine; 🇺🇸 Columbia, Missouri, United States

Northeast Regional Epilepsy Group; 🇺🇸 Hackensack, New Jersey, United States

St. Peters Hospital; 🇺🇸 New Brunswick, New Jersey, United States

Montefiore; 🇺🇸 Bronx, New York, United States

Duke University Clinical Research at Pickett Road; 🇺🇸 Durham, North Carolina, United States

Wake Forest University - School of Medicine; 🇺🇸 Winston-Salem, North Carolina, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Austin Epilepsy Care Center - Clinic/Outpatient Facility; 🇺🇸 Austin, Texas, United States

Neurology Consultants of Dallas, PA - Hospital; 🇺🇸 Dallas, Texas, United States

Virginia Epilepsy and Neurodevelopmental Clinic at WNC; 🇺🇸 Winchester, Virginia, United States

Hospital de Ninos de La Santisma Trinidad; 🇦🇷 Córdoba, Cordoba, Argentina

Resolution Psychopharmacology Research Institute; 🇦🇷 Mendoza, Argentina

Austin Hosptial; 🇦🇺 Heidelberg, Australia

Alfred Health; 🇦🇺 Melbourne, Australia

Perth's Children Hospital; 🇦🇺 Nedlands, Australia

Queensland Children's Hospital; 🇦🇺 South Brisbane, Australia

Fundacion Hospital Universidad del Norte; 🇨🇴 Barranquilla, Colombia

Fundacion Valle del Lili/Clinic - Outpatient; 🇨🇴 Cali, Colombia

CliniSalud del Sur S.A.S - Centro de Investigación; 🇨🇴 Envigado, Colombia

Hospital Pabloe Tubon Uribe; 🇨🇴 Medellín, Colombia

Institutio Neurologico de Colombia; 🇨🇴 Medellín, Colombia

Universitatsklinikum Erangen; 🇩🇪 Erlangen, Bayern, Germany

Kleinwachau Sächsisches Epilepsiezentrum; 🇩🇪 Radeberg, Sachsen, Germany

Iaso Children's Hospital; 🇬🇷 Maroúsi, Attiki, Greece

Orszagos Mentalis, Ideggyogyaszati es Idegsebezeti Intezet; 🇭🇺 Budapest, Hungary

Semmelweis Egyetem Idegsebeszeti es Neurointervencios Klinika; 🇭🇺 Budapest, Hungary

Tela Viv Sourlasky Medical Center; 🇮🇱 Tel Aviv Yafo, Tel Aviv, Israel

Soroka University Medical Centre; 🇮🇱 Be'er Sheva, Israel

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN; 🇮🇹 Genova, Liguria, Italy

ASST Fatebenefratelli Sacco - Ospedale dei Bambini Vittore Buzzi; 🇮🇹 Milano, Lombardia, Italy

Fondazione IRCCS Di Rilievo Nazionale Instituto; 🇮🇹 Milano, Lombardia, Italy

Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN; 🇮🇹 Firenze, Italy

ASST Santi Paolo E Carlo - Azienda Universitaria-Polo Universitaria - San Paolo; 🇮🇹 Milano, Italy

Azienda Ospedaliera Universitaria Integrata Di Verona; 🇮🇹 Verona, Italy

Kyungpook National University Chilgok Hospital; 🇰🇷 Daegu, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Civil Fray Antonio Alcalde; 🇲🇽 Guadalajara, Jalisco, Mexico

Neurociencias Estudios Clinicos S.C.; 🇲🇽 Culiacán, Mexico

Clinstile, S.A. de C.V.; 🇲🇽 Mexico City, Mexico

Szpital Kliniczny im.H.Swiecickiego Uniwersytetu Medycznego im.K.Marcinkowskiego w Poznaniu-Dluga1/2; 🇵🇱 Poznan, Wielkopolskie, Poland

Centrum Medyczne Plejady; 🇵🇱 Kraków, Poland

Hospital Garcia de Orta; 🇵🇹 Almada, Setubal, Portugal

Centro Hospitalar de Lisboa Norte, EPE; 🇵🇹 Lisboa, Portugal

Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier; 🇵🇹 Lisboa, Portugal

Centro Hospitalar de Sao Joao, EPE; 🇵🇹 Porto, Portugal

Childrens University Hospital; 🇷🇸 Belgrade, Serbia

University Clinical Center of Serbia - PPDS; 🇷🇸 Belgrade, Serbia

University Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

University Clinical Center Nis; 🇷🇸 Niš, Serbia

Children and Youth Health Care Institute of Vojvodina; 🇷🇸 Novi Sad, Serbia

Hospital Sant Joan de Deu - PIN; 🇪🇸 Esplugues De Llobregat, Barcelona, Spain

Hospital Infantil Universitario Niño Jesus - PIN; 🇪🇸 Madrid, Spain

Hospital Ruber Internacional (Grupo Quironsalud); 🇪🇸 Madrid, Spain

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital; 🇨🇳 Taoyuan, Taiwan