"Open-Label Safety and Efficacy Study of Cenobamate (YKP3089) in Children with Partial-onset (Focal) Seizures "

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sk Life Science Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

22 Mar 2023 → ongoing

Decision date (initial)

2024-04-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-506841-52-00

EudraCT number

2020-005344-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

"To evaluate the safety and tolerability of cenobamate in pediatric subjects 2<18 years of age with partial-onset (focal) seizures "

Secondary objectives 4

1. To evaluate the efficacy of cenobamate in pediatric subjects with partial onset (focal) seizures
2. To collect plasma samples to support the evaluation of the pharmacokinetics (PK) of cenobamate in pediatric subjects with partial onset (focal) seizures administered with tablets or suspension
3. To collect plasma samples to support the evaluation of the PK/pharmacodynamics (PD) of cenobamate in pediatric subjects with partial onset (focal) seizures
4. Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral suspension and tablets – Day 1, and Day 15.

Conditions and MedDRA coding

partial-onset (focal) seizures

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002563-PIP02-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Have a diagnosis of epilepsy with partial-onset (focal) seizures (POS) with or without secondarily generalized seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures. For participants aged 6 to less than 18 years a diagnosis should have been established at least 12 months prior to Visit 1 (Screening). For participants aged 2 to less than 6 years, a diagnosisshould have been established at least 1 month prior to Visit 1 (Screening). Diagnosis should be supported by clinical history and an electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (i.e., clinical history)
2. Male or female participant, from age 2 to less than 18 years at the time of informed consent/assent (dates including informed consent in YKP3089C039)
3. Have a minimum weight of 10.0 kilograms (kg) (27.0 pounds [lb])
4. Have had a brain imaging (e.g., magnetic resonance imaging [MRI] scan or computed tomography (CT) within 10 years before Visit 1 (Screeining) that ruled out a progressive cause of epilepsy
5. For subjects new to Study YKP3089C040 participants must have had at least 1 POS seizure during the 28-day Baseline Period. Only simple POS with motor signs, complex POS, and complex POS with secondary generalization are counted toward this inclusion for POS
6. Are currently being treated with stable doses of 1 to a maximum of 3 approved antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before to Visit 1 (Screening). A vagal nerve stimulator [VNS] will not be counted as one of the 3 allowed AEDs, but the settings should be stable for at least 4 weeks prior to Visit 1 (Screening).
7. Investigator believes subject could benefit from new or continued exposure to study drug
8. Subjects entering from study YKP3089C039 must continue to meet all of the inclusion criteria from the YKP3089C039 study
9. Subjects receiving felbamate as a concomitant AED must meet the following criteria: a. Have a 12-month history of felbamate use and a history of a fixed dosing regimen for a minimum of 60 days prior to Visit 1 (Screening). b. No prior or known history of hepatotoxicity or hematologic disorder due to felbamate.
10. Subjects following a ketogenic diet will be allowed as long as the diet has been stable for at least 30 days prior to Visit 1 (Screening) and will remain stable for the duration of the study Any potential exception to inclusion criteria allowing de minimis (clinically trivial and meaningless) variations must be approved by the medical monitor.

Exclusion criteria 24

1. Females who are breastfeeding or pregnant at Screening or Baseline
2. Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 2 years before Visit 1 (Screening).
3. Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1 (Screening).
4. Have an unstable psychiatric diagnosis that may confound participants' ability to participate in the study or that may prevent completion of the protocol-specified tests (e.g., significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1 (Screening), current psychotic disorder, acute mania).
5. 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 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) in participants aged 6 and above.
6. Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1 (Screening); however, those who have previously documented "failed" epilepsy surgery will be allowed.
7. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
8. Presence of only nonmotor simple partial seizures or primary generalized epilepsies.
9. Evidence of moderate or severe renal insufficiency as defined by estimated glomerular filtration rates (eGFRs) of 31 to < 60 "milliliters per minute (mL/min)" and < 30 mL/min, respectively.
10. Evidence of significant active hepatic disease. Stable elevation of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) due to concomitant medication(s), will be allowed if they are less than 3 times the upper limit of normal (ULN).
11. Evidence of significant active hematological disease; white blood cell (WBC) count equal or less than 2500/μL (2.50 1E+09/liter [L]) or an absolute neutrophil count equal or less than 1000/μL (1.00 1E+09/L).
12. Subjects with Familial short QT syndrome
13. Clinically significant electrocardiogram (ECG) abnormality, including prolonged corrected QT interval (QTc) defined as greater than 450 milliseconds (msec) or shortened corrected QT interval (QTc) defined as less than 340 msec.
14. Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
15. Subject has a history of any serious drug-induced hypersensitivity reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermal necrolysis, or DRESS) or any drug-related rash requiring hospitalization.
16. History of AED-associated rash that involved conjunctiva or mucosae.
17. History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication.
18. Concomitant use of vigabatrin. Participants who took vigabatrin in the past must be off vigabatrin for at least 5 months before Visit 1 (Screeining) and with documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in a visual perimetry test.
19. A history of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period is considered a 1-time rescue) more than once within the 30 days prior to Visit 1 (Screening).
20. A VNS implanted less than 5 months before Visit 1 (Screening) or changes in parameter less than 4 weeks before Visit 1 (or thereafter during the study)
21. History of or a concomitant medical condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study or compromise the participant's ability to safely complete the study.
22. Have participated in a study involving administration of an investigational drug or device within 4 weeks before Visit 1 (Screening), or within approximately 5 half-lives of the previous investigational compound, whichever is longer.
23. Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
24. For subjects new to Study YKP3089C040 previous exposure to cenobamate or sensitivity/allergy to components of the oral suspension. Any potential exception to exclusion criteria allowing de minimis (clinically trivial and meaningless) variations must be approved by the medical monitor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of participants with any treatment-emergent adverse event (TEAE) and any serious adverse event (SAE) during the first year of exposure

Secondary endpoints 10

1. Percent change in seizure frequency over 28 days during the Treatment Period and during each phase of the study
2. Number of participants who are seizure-free during the Treatment Period and during each phase of the study
3. Percentage of responders (50%, 75%, and 90% responders) during the Treatment Period and during each phase of the study
4. Change from Baseline in A-B neuropsychological assessment schedule (ABNAS) end of titration, end of maintenance and 52 weeks
5. Change from Baseline in Child Behavior Checklist (CBCL) scores end of titration, end ofmaintenance and 52 weeks
6. Change from Baseline in Lafayette Grooved Pegboard Test (LGPT) scores end of titration, end of maintenance and 52 weeks
7. Change from Baseline in height
8. Change from Baseline in weight
9. Percentage of participants with any treatment-emergent reports of suicidal ideation and behavior assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) during treatment (adult version for 12-18 year olds; Pediatric version for 6-11 year olds) 32
10. Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral suspension and tablets Visit 2 and Visit 3.

Investigational products

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

Test 5

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

Pranoti Pradhan, MD

Public contact point

Organisation

Sk Life Science Inc.

Contact name

Pranoti Pradhan, MD

Third parties 9

Locations

4 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 77 files

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

Application history

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