Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults

NCT05219617 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: YKP509C003
• Study Type: interventional
• Target: 252
• Locations: 16 countries
• Sites: 71

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).

Conditions

Seizures; Lennox Gastaut Syndrome

Keywords

Seizures; Lennox Gastaut Syndrome; Pediatrics; Adults

Outcome Measures

Primary Outcomes (1)

• 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.

  Efficacy of Carisbamate YKP509

  3 years

Secondary Outcomes (3)

• 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

• Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period.

  3 years

• Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit.

  3 years

Other Outcomes (5)

• Percentage change from baseline in the 28-day frequency of: drop seizures (tonic, atonic, tonic-clonic); non-drop seizures (myoclonic seizures, atypical absence); total seizures during the maintenance phase of the double-blind treatment period.

  3 years

• Percentage change from baseline in non-drop seizures (myoclonic seizures, atypical absence) frequency per 28 days during the during the double-blind treatment period.

  3 years

• 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 maintenance phase of the double-blind treatment period.

  3 years

Study Arms (4)

Carisbamate 200 mg BID arm

EXPERIMENTAL

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

Drug: Carisbamate

Carisbamate 300 mg BID arm

EXPERIMENTAL

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

Drug: Carisbamate

Placebo matched to 200 mg BID arm

PLACEBO COMPARATOR

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

Drug: Carisbamate

Placebo matched to 300 mg BID arm

PLACEBO COMPARATOR

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

Drug: Carisbamate

Interventions

Carisbamate DRUG

Adolescent subjects 12 to 18 years old will receive the same dose as adults. Subjects 4 to \< 12 years old in the carisbamate 200 mg BID arm will receive 4 mg/kg BID (not to exceed 200 mg BID \[or a total of 400 mg per day\]). Subjects 4 to \< 12 years old in the carisbamate 300 mg BID arm will receive 5.5 mg/kg BID (not to exceed 300 mg BID \[or a total of 600 mg per day\]).

Carisbamate 200 mg BID arm; Carisbamate 300 mg BID arm; Placebo matched to 200 mg BID arm; Placebo matched to 300 mg BID arm

Eligibility Criteria

• Age: 4 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject must have a documented history of Lennox-Gastaut syndrome by:
• Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure
• History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern \<3.0 Hz)
• History of developmental delay
• Male or female subjects
• Subjects must be age 4-55 years at the time of consent/assent
• Must have been \<11 years old at the onset of LGS
• 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).
• 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
• 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.
• 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.
• Parents or caregivers must be able to keep accurate seizure diaries
• 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.
• Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study
• Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements

You may not qualify if:

• 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
• 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
• Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline
• Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling
• Current use of felbamate with less than 18 months of continuous exposure
• 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.
• Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline
• Status epilepticus within 12 weeks prior to Visit 1
• Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator
• Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2)
• 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
• 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.
• Subject is pregnant, may be pregnant, lactating or planning to be pregnant
• 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
• 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.

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (71)

Stanford University Hospital

Palo Alto, California, 94305, United States

RECRUITING

University of Florida Health Science Center

Jacksonville, Florida, 32209, United States

COMPLETED

AdventHealth

Orlando, Florida, 32803, United States

COMPLETED

Pediatric Epilepsy and Neurology Specialists

Tampa, Florida, 33609, United States

RECRUITING

University of South Florida

Tampa, Florida, 33620, United States

COMPLETED

Axcess Medical Research

Wellington, Florida, 33414, United States

COMPLETED

Consultants in Epilepsy and Neurology PLLC

Boise, Idaho, 83702, United States

COMPLETED

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, 40504, United States

COMPLETED

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

COMPLETED

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

COMPLETED

University of Missouri School of Medicine

Columbia, Missouri, 65211, United States

COMPLETED

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

RECRUITING

St. Peters Hospital

New Brunswick, New Jersey, 08901, United States

COMPLETED

Montefiore

The Bronx, New York, 10467, United States

COMPLETED

Duke University Clinical Research at Pickett Road

Durham, North Carolina, 27713, United States

RECRUITING

Wake Forest University - School of Medicine

Winston-Salem, North Carolina, 27101, United States

COMPLETED

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Austin Epilepsy Care Center - Clinic/Outpatient Facility

Austin, Texas, 78758, United States

COMPLETED

Neurology Consultants of Dallas, PA - Hospital

Dallas, Texas, 75231, United States

COMPLETED

Virginia Epilepsy and Neurodevelopmental Clinic at WNC

Winchester, Virginia, 22601, United States

COMPLETED

Hospital de Ninos de La Santisma Trinidad

Córdoba, Córdoba Province, Argentina

COMPLETED

Resolution Psychopharmacology Research Institute

Mendoza, Mendoza Province, Argentina

COMPLETED

Austin Hosptial

Heidelberg, Australia

RECRUITING

Alfred Health

Melbourne, Australia

RECRUITING

Perth's Children Hospital

Nedlands, Australia

COMPLETED

Queensland Children's Hospital

South Brisbane, Australia

COMPLETED

Fundacion Hospital Universidad del Norte

Barranquilla, Colombia

WITHDRAWN

Fundacion Valle del Lili/Clinic - Outpatient

Cali, Colombia

WITHDRAWN

CliniSalud del Sur S.A.S - Centro de Investigación

Envigado, Colombia

COMPLETED

Hospital Pabloe Tubon Uribe

Medellín, Colombia

COMPLETED

Institutio Neurologico de Colombia

Medellín, Colombia

RECRUITING

Universitatsklinikum Erangen

Erlangen, Bavaria, Germany

RECRUITING

Kleinwachau Sächsisches Epilepsiezentrum

Radeberg, Saxony, Germany

RECRUITING

Iaso Children's Hospital

Marousi, Attica, Greece

RECRUITING

Orszagos Mentalis, Ideggyogyaszati es Idegsebezeti Intezet

Budapest, Hungary

COMPLETED

Semmelweis Egyetem Idegsebeszeti es Neurointervencios Klinika

Budapest, Hungary

RECRUITING

Tela Viv Sourlasky Medical Center

Tel Aviv, Tel Aviv, Israel

COMPLETED

Soroka University Medical Centre

Beersheba, Israel

COMPLETED

Hadassah Medical Center

Jerusalem, 91220, Israel

COMPLETED

Sheba Medical Center

Ramat Gan, Israel

COMPLETED

Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN

Genoa, Liguria, Italy

RECRUITING

ASST Fatebenefratelli Sacco - Ospedale dei Bambini Vittore Buzzi

Milan, Lombardy, Italy

RECRUITING

Fondazione IRCCS Di Rilievo Nazionale Instituto

Milan, Lombardy, Italy

RECRUITING

Azienda Ospedaliera Universitaria Integrata Di Verona

Verona, Verona, Italy

RECRUITING

Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN

Florence, Italy

RECRUITING

ASST Santi Paolo E Carlo - Azienda Universitaria-Polo Universitaria - San Paolo

Milan, Italy

COMPLETED

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

RECRUITING

Neurociencias Estudios Clinicos S.C.

Culiacán, Mexico

RECRUITING

Clinstile, S.A. de C.V.

Mexico City, 06700, Mexico

RECRUITING

Szpital Kliniczny im.H.Swiecickiego Uniwersytetu Medycznego im.K.Marcinkowskiego w Poznaniu-Dluga1/2

Poznan, Greater Poland Voivodeship, Poland

COMPLETED

Centrum Medyczne Plejady

Krakow, Poland

RECRUITING

Centro Hospitalar de Lisboa Norte, EPE

Lisbon, Lisbon District, Portugal

RECRUITING

Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier

Lisbon, Lisbon District, Portugal

COMPLETED

Centro Hospitalar de Sao Joao, EPE

Porto, Porto District, Portugal

RECRUITING

Hospital Garcia de Orta

Almada, Setúbal District, Portugal

COMPLETED

Childrens University Hospital

Belgrade, Belgrade, Serbia

RECRUITING

University Clinical Center of Serbia - PPDS

Belgrade, Serbia

RECRUITING

University Clinical Center Kragujevac

Kragujevac, Serbia

RECRUITING

University Clinical Center Nis

Niš, Serbia

RECRUITING

Children and Youth Health Care Institute of Vojvodina

Novi Sad, Serbia

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, Barcelona, Spain

COMPLETED

Hospital Infantil Universitario Niño Jesus - PIN

Madrid, Spain

RECRUITING

Hospital Ruber Internacional (Grupo Quironsalud)

Madrid, Spain

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Taiwan

RECRUITING

Chang Gung Memorial Hospital

Taoyuan District, Taiwan

COMPLETED

MeSH Terms

Conditions

Seizures; Lennox Gastaut Syndrome

Interventions

S-2-O-carbamoyl-1-o-chlorophenyl-ethanol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Marc Kamin, MD

  SK Life Science, Inc.

  STUDY DIRECTOR

Central Study Contacts

Barbara Remes

CONTACT

201-421-3810; bremes@sklsi.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This double-blind, randomized, placebo-controlled study will evaluate the efficacy of carisbamate 200 mg BID or the pediatric equivalent dose and 300 mg BID or the pediatric equivalent dose for the treatment of seizures associated with Lennox Gastaut syndrome in subjects 4 to 55 years of age.

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: February 2, 2022
• Study Start: April 28, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

IL (4); ES (3); GR (1); SE (5); HU (2); KR (3); PL (2); US (22); IT (6); PT (4); CO (5); AU (4); AR (2); DE (2); TW (3); ME (3)