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

PHASE3RECRUITING

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).

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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

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

History of COVID-19 vaccination is permitted

Exclusion criteria

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.

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

Subject with total bilirubin [TBL] >2 x ULN (except for Gilbert's syndrome).

Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1)

History of positive antibody/antigen test for human immunodeficiency virus (HIV)

If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products

Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study

Subject who has taken or used any investigational drug or device in the 4 weeks prior to the screening visit (Visit 1)

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

Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome

Subject with a short QTc interval (<340 msec) or long QTc interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG)

Benzodiazepine rescue administered on average more than once a week in the month before Visit 1

Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.

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Eligibility

Age eligible for study : 4 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-04-28

Primary completion: 2025-06-01

Study completion finish: 2026-06-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT05219617

Intervention or treatment

DRUG: Carisbamate

Conditions

• Seizures
• Lennox Gastaut Syndrome

Condition: Seizures, Lennox Gastaut Syndrome
DRUG: Carisbamate
Heidelberg, Not Specified, Australia and more
Sponsor: SK Life Science, Inc.

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Find a site

Closest Location:

Austin Hosptial

Research sites nearby

Select from list below to view details:

Austin Hosptial
Heidelberg, Not Specified, Australia
Alfred Health
Melbourne, Not Specified, Australia
Perth's Children Hospital
Nedlands, Not Specified, Australia
Queensland Children's Hospital
South Brisbane, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Carisbamate 200 mg BID arm 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 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 \[or a total of 600 mg per day\]).
EXPERIMENTAL: Carisbamate 300 mg BID arm 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 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 \[or a total of 600 mg per day\]).
PLACEBO_COMPARATOR: Placebo matched to 200 mg BID arm 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 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 \[or a total of 600 mg per day\]).
PLACEBO_COMPARATOR: Placebo matched to 300 mg BID arm 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 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 \[or a total of 600 mg per day\]).

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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
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
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

Frequently Asked Questions

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References

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