A clinical study to evaluate safety and efficacy of Caribasmate

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sk Life Science Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

31 Mar 2023 → ongoing

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

SK Life Science, Inc.

External identifiers

EU CT number

2023-506616-41-00

EudraCT number

2022-001256-42

ClinicalTrials.gov

NCT05219617

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Others

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

Secondary objectives 1

1. "• 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."

Conditions and MedDRA coding

Lennox-Gastaut syndrome (LGS)

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 1. Subject must have a documented history of Lennox-Gastaut syndrome by: a. Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure b. History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern <3.0 Hz) c. 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 8 drop seizures with potential to fall (tonic, atonic, tonic-clonic) during the 4-week Baseline period preceding randomization (minumim of 4 drop seizures in the first two weeks and 4 in the last two weeks). Drop seizures are defined as a countable 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).
2. 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 2 weeks after dose of study drug. 11. Subject and/or caregiver/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 3

1. 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 tumor2. 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 12 months of continuous exposure 6. Subjects who took vigabatrin in the past must have discontinued it at least 5 months before Visit 1. Subjects taking vigabatrin should have documentation showing no evidence of a vigabatrin-associated visual field abnormality. 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)
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 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 question 4 or 5 in the Suicidal Ideation section of the age specific Columbia-Suicide Severuty Rating Scale (C-SSRS) in subjects aged 6 years and above who are able to be evaluated. 15. Any suicidal behavior within 2 years before Visit 2 (i.e., answering YES to any questions in the Suicidal behavior section of the age-specifc 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
3. 21. Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study 22. Subject who has participated in any clinical study of an investigational product or device in the 30 days prior to the screening visit (Visit 1) 23. Concomitant use of medications known to be strong inducers of cytochrome UGT enzymes 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 QTcF interval (<340 msec) or long QTcF interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG) 26. Intermittent benzodiazepine rescue administered more than four times in the 28 days prior to Visit 1 (1 to 2 doses in a 24-hour period is considered as one rescue). 27. Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The 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) during the double-blind treatment period.

Secondary endpoints 4

1. 1. The percentage of subjects with at least a 50% reduction from baseline in the total frequency of countable drop seizures (tonic, atonic, tonic-clonic) during the double-blind treatment period.
2. 2. Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period.
3. 3. Subject/Caregiver Global Impression of Change in overall condition (S/CGI-C) score at the last visit.
4. Please refer to the Protocol for further Secondary endpoints.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sk Life Science Inc.

Sponsor organisation

Sk Life Science Inc.

Address

461 From Road Fl 5

City

Paramus

Postcode

07652-3524

Country

United States

Scientific contact point

Organisation

Sk Life Science Inc.

Contact name

Sunita Misra

Public contact point

Organisation

Sk Life Science Inc.

Contact name

Sunita Misra

Third parties 7

Locations

7 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications