Seizures Clinical Trial
Official title:
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults, With Optional Open-Label Extension
Verified date | May 2024 |
Source | SK Life Science, Inc. |
Contact | Barbara Remes |
Phone | 201-421-3810 |
bremes[@]sklsi.com | |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Recruiting |
Enrollment | 252 |
Est. completion date | June 2026 |
Est. primary completion date | June 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 4 Years to 55 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Argentina | Hospital de Ninos de La Santisma Trinidad | Córdoba | Cordoba |
Argentina | Resolution Psychopharmacology Research Institute | Mendoza | |
Australia | Austin Hosptial | Heidelberg | |
Australia | Alfred Health | Melbourne | |
Australia | Perth's Children Hospital | Nedlands | |
Australia | Queensland Children's Hospital | South Brisbane | |
Colombia | 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 | |
Germany | Universitatsklinikum Erangen | Erlangen | Bayern |
Germany | Kleinwachau Sächsisches Epilepsiezentrum | Radeberg | Sachsen |
Greece | Iaso Children's Hospital | Maroúsi | Attiki |
Israel | Soroka University Medical Centre | Be'er Sheva | |
Israel | Hadassah Medical Center | Jerusalem | |
Israel | Sheba Medical Center | Ramat Gan | |
Israel | Tela Viv Sourlasky Medical Center | Tel Aviv Yafo | Tel Aviv |
Italy | Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN | Calambrone | |
Italy | Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN | Genova | Liguria |
Italy | ASST Fatebenefratelli Sacco - Ospedale dei Bambini Vittore Buzzi | Milano | Lombardia |
Italy | ASST Santi Paolo E Carlo - Azienda Universitaria-Polo Universitaria - San Paolo | Milano | |
Italy | Fondazione IRCCS Di Rilievo Nazionale Instituto | Milano | Lombardia |
Italy | Azienda Ospedaliera Universitaria Integrata Di Verona | Verona | |
Korea, Republic of | Kyungpook National University Chilgok Hospital | Daegu | |
Korea, Republic of | Samsung Medical Center | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Mexico | Neurociencias Estudios Clinicos S.C. | Culiacán | |
Mexico | Hospital Civil Fray Antonio Alcalde | Guadalajara | Jalisco |
Mexico | Clinstile, S.A. de C.V. | Mexico City | |
Poland | Centrum Medyczne Plejady | Kraków | |
Poland | Szpital Kliniczny im.H.Swiecickiego Uniwersytetu Medycznego im.K.Marcinkowskiego w Poznaniu-Dluga1/2 | Poznan | Wielkopolskie |
Portugal | 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 | |
Serbia | 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 | |
Spain | 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 | |
Taiwan | National Taiwan University Hospital | Taipei | |
Taiwan | Taipei Veterans General Hospital | Taipei | |
Taiwan | Chang Gung Memorial Hospital | Taoyuan | |
United States | Austin Epilepsy Care Center - Clinic/Outpatient Facility | Austin | Texas |
United States | Johns Hopkins Hospital | Baltimore | Maryland |
United States | Mid-Atlantic Epilepsy and Sleep Center | Bethesda | Maryland |
United States | Consultants in Epilepsy and Neurology PLLC | Boise | Idaho |
United States | Montefiore | Bronx | New York |
United States | University of Missouri School of Medicine | Columbia | Missouri |
United States | Neurology Consultants of Dallas, PA - Hospital | Dallas | Texas |
United States | Duke University Clinical Research at Pickett Road | Durham | North Carolina |
United States | Northeast Regional Epilepsy Group | Hackensack | New Jersey |
United States | University of Florida Health Science Center | Jacksonville | Florida |
United States | Bluegrass Epilepsy Research, LLC | Lexington | Kentucky |
United States | St. Peters Hospital | New Brunswick | New Jersey |
United States | University Medical Center New Orleans | New Orleans | Louisiana |
United States | AdventHealth | Orlando | Florida |
United States | Stanford University Hospital | Palo Alto | California |
United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Mayo Clinic | Rochester | Minnesota |
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 | Virginia Epilepsy and Neurodevelopmental Clinic at WNC | Winchester | Virginia |
United States | Wake Forest University - School of Medicine | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
SK Life Science, Inc. |
United States, Argentina, Australia, Colombia, Germany, Greece, Israel, Italy, Korea, Republic of, Mexico, Poland, Portugal, Serbia, Spain, Taiwan,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | 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. | Efficacy of Carisbamate YKP509 | 3 years | |
Other | Percentage change from baseline in non-drop seizures (myoclonic seizures, atypical absence) frequency per 28 days during the during the double-blind treatment period. | Efficacy of Carisbamate YKP509 | 3 years | |
Other | 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. | Efficacy of Carisbamate YKP509 | 3 years | |
Other | Proportion of subjects with a 75%, 90% and 100% response rate for drop seizures (tonic, atonic, tonic-clonic), non-drop seizures, and total seizures during the double-blind treatment period. | Efficacy of Carisbamate YKP509 | 3 years | |
Other | Proportion of subjects with a 75%, 90% and 100% response rate for drop seizures (tonic, atonic, tonic-clonic), non-drop seizures, and total seizures during the maintenance phase of the double-blind treatment period. | Efficacy of Carisbamate YKP509 | 3 years | |
Primary | 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 | 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. | Efficacy of Carisbamate YKP509 | 3 years | |
Secondary | Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period. | Efficacy of Carisbamate YKP509 | 3 years | |
Secondary | Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit. | Efficacy of Carisbamate YKP509- Scoring will be from 1 to 7 with 1 (very much improved) to 7 (very much worse) | 3 years |
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