Cenobamate for Epilepsy

Recruiting at 48 trial locations

Overseen By Temitayo Oyegbile-Chidi, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: SK Life Science, Inc.

Must be taking: Antiepileptic drugs

Must not be taking: Vigabatrin, Rescue benzodiazepines

Disqualifiers: Pregnancy, Pseudo-seizures, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called cenobamate to determine its safety and tolerability in children and teens aged 2 to 17 with epilepsy characterized by partial-onset seizures. These seizures begin in a specific brain area and may spread. Participants should have experienced these seizures for at least a year and be on stable doses of one to three seizure medications. The trial aims to assess whether cenobamate could serve as a helpful new treatment for managing seizures in young people. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for epilepsy.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. Participants must be on stable doses of 1 to 3 approved antiepileptic drugs for at least 4 weeks before starting the trial.

Is there any evidence suggesting that cenobamate is likely to be safe for humans?

Studies have shown that cenobamate is a promising treatment for managing focal (partial-onset) seizures. Research indicates that adults generally tolerate cenobamate well, with some experiencing mild to moderate side effects. For instance, the rate of discontinuation due to side effects was 11% for a 100 mg dose, 9% for a 200 mg dose, and 21% for a 400 mg dose. In comparison, 4% of those not taking cenobamate stopped their treatment.

Long-term studies have confirmed that cenobamate is safe for adults and can help reduce the number of seizures. Although cenobamate is currently approved for adults with epilepsy, this trial aims to test its safety specifically in children aged 2 to 17 years. Since it is already approved for adults, there is a strong reason to believe it might be safe for children too, but this study will provide more definite answers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for epilepsy?

Cenobamate is unique because it offers a new hope for epilepsy patients by potentially reducing seizures more effectively than current treatments like valproate, carbamazepine, and lamotrigine. Researchers are excited because cenobamate acts on two different pathways in the brain, combining sodium channel inhibition with positive modulation of GABA-A receptors. This dual action could mean better seizure control with fewer side effects, making it a promising option for those who haven't found success with existing medications.

What evidence suggests that cenobamate might be an effective treatment for epilepsy?

Studies have shown that cenobamate effectively manages focal onset seizures. In one study, over 20% of individuals with drug-resistant epilepsy stopped having seizures entirely after using cenobamate. Another study found that adding cenobamate reduced seizure frequency by 50% or more in 62% of patients. Additionally, long-term research indicates that cenobamate remains safe and effective in reducing seizures over time. This trial will evaluate cenobamate in different age groups, suggesting it could be a promising option for treating partial-onset seizures in children. ^{2 5 6 7 8}

Who Is on the Research Team?

Marc Kamin, MD

Principal Investigator

SK Life Science, Inc.

Are You a Good Fit for This Trial?

This trial is for children aged 2-17 with partial-onset seizures and a stable epilepsy diagnosis. They must weigh at least 10 kg, have had an MRI or CT scan within the last 10 years, be on a steady dose of up to three antiepileptic drugs (excluding VNS), and may also be on a ketogenic diet. Pregnant or breastfeeding females, those with certain psychiatric conditions, significant diseases, recent investigational drug use, specific genetic intolerances or severe renal/hepatic insufficiency are excluded.

Inclusion Criteria

I have never had liver or blood problems from taking felbamate.

I have been diagnosed with epilepsy that starts in one area of my brain for over a year.

I have been taking felbamate for at least a year and have been on a stable dose for the last 60 days.

Exclusion Criteria

I've used emergency anxiety medication more than once in the last month.

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).

I have been diagnosed with Familial Short QT Syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cenobamate tablets and suspension to evaluate safety, tolerability, and efficacy

3 years

Regular visits for safety and efficacy assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cenobamate

Trial Overview The study tests the safety and effectiveness of Cenobamate (Xcopri) in young patients with focal seizures. It aims to see how well they tolerate this medication and if it helps control their seizures better than their current treatment regimen.

How Is the Trial Designed?

Group I: 6 to <12 years old Experimental Treatment 1 Intervention

Group II: 4 to <6 years old Experimental Treatment 1 Intervention

Group III: 2 to <4 years old Experimental Treatment 1 Intervention

Group IV: 12 to < 18 year olds Experimental Treatment 1 Intervention

Cenobamate is already approved in United States, European Union, United Kingdom, Canada for the following indications:

Approved in United States as Xcopri for:

• Partial-onset seizures in adults

Approved in European Union as Ontozry for:

• Adjunctive treatment of focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medications

Approved in United Kingdom as Ontozry for:

• Add-on treatment for focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least one other add-on treatment

Approved in Canada as Ontozry for:

• Adjunctive treatment of focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medications

Who Is Running the Clinical Trial?

SK Life Science, Inc.

Lead Sponsor

Trials

42

Recruited

8,900+

Published Research Related to This Trial

Cenobamate (CNB) demonstrated long-term efficacy in reducing seizure frequency, with a median reduction of 76.1% at 43-48 months, and 16.4% of patients achieving complete seizure freedom during this period.

The treatment was well-tolerated over the long term, with retention rates of 71% at 24 months and no new safety issues identified, although common adverse events included dizziness and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. Klein, P., Aboumatar, S., Brandt, C., et al.[2022]

Cenobamate (CNB) shows promise as an effective antiseizure medication for patients with drug-resistant genetic generalized epilepsies (GGE) and combined generalized and focal epilepsies (CGFE), with a mean seizure reduction of 58% and a 70% responder rate in a retrospective review of 13 patients.

No patients experienced worsening of generalized-onset seizures while on CNB, although 77% reported side effects, indicating the need for careful management of treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy. Agashe, S., Worrell, G., Britton, J., et al.[2023]

Cenobamate (XCOPRI®) is a newly approved oral medication for treating partial-onset seizures in adults, developed by SK Life Science Inc. and Arvelle Therapeutics.

The approval was based on positive results from two pivotal phase 2 trials, highlighting its efficacy as a neurotherapeutic option for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate: First Approval. Keam, SJ.[2020]

Cenobamate, an antiepileptic drug approved for focal seizures, demonstrated a favorable safety profile in a study involving 210 healthy subjects, with most treatment-emergent adverse events being mild and no deaths reported.

The pharmacokinetics of cenobamate support once-daily dosing, as it showed dose-proportional increases in plasma concentration and a long half-life of 30 to 76 hours, making it a convenient option for managing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending-Dose Studies in Healthy Subjects. Vernillet, L., Greene, SA., Kamin, M.[2021]

Cenobamate, an investigational drug, significantly reduced the frequency of focal seizures in patients with uncontrolled epilepsy, showing a dose-dependent effect with the highest reduction observed at 400 mg (55% decrease in seizure frequency).

While cenobamate was effective, treatment-emergent adverse events were more common at higher doses, with 90% of patients in the 400 mg group experiencing side effects, indicating a need for careful monitoring at increased dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Krauss, GL., Klein, P., Brandt, C., et al.[2020]

In a study of 51 patients with highly refractory focal epilepsy, cenobamate demonstrated an 80.4% retention rate at the last follow-up, indicating its effectiveness in long-term treatment.

The treatment resulted in a 56.5% responder rate for focal seizures and a 63.6% responder rate for focal to bilateral tonic-clonic seizures at three months, with a manageable safety profile as 43.1% of patients reported treatment-emergent adverse events, most of which resolved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study. Beltrán-Corbellini, Á., Romeral-Jiménez, M., Mayo, P., et al.[2023]

Cenobamate, a new antiseizure medication, was found to be rapidly absorbed and well-tolerated in healthy Japanese subjects, with a maximum plasma concentration reached within 0.75 to 2.25 hours after a single oral dose.

The pharmacokinetics of cenobamate in Japanese individuals showed similar patterns to those observed in non-Japanese subjects, indicating comparable systemic exposure and safety across different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of cenobamate, a novel antiseizure medication, in healthy Japanese, and an ethnic comparison with healthy non-Japanese. Yang, E., Sunwoo, J., Huh, KY., et al.[2022]

In a retrospective study of 45 patients, cenobamate was found to be effective for treating focal seizures, with a 60% response rate among participants, supporting its use beyond initial clinical trials.

Notably, patients with a history of drug-related rashes did not experience any rashes while on cenobamate, indicating it may be a safe option for this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Real-World Experience With Cenobamate in Adolescents and Adults: A Single Center Experience. Elliott, T., Ridley-Pryor, T., Gienapp, AJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10456719/

Cenobamate (YKP3089) and Drug-Resistant Epilepsy CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure ...

2. seizure-journal.com seizure-journal.com/article/S1059-1311(25)00110-4/fulltext

Efficacy and safety of Cenobamate: a multicenter ... The addition of cenobamate resulted in a ≥ 50 % reduction in seizure frequency in 62 % of patients, with 16.5 % achieving seizure freedom by the ...

3. xcoprihcp.com xcoprihcp.com/efficacy/

XCOPRI® (cenobamate tablets) CV Efficacy Primary outcome: Patients taking XCOPRI experienced up to 2x greater seizure reduction compared with placebo (55% XCOPRI 400 mg, 55% XCOPRI 200 mg, 36 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11263269/

Evidence from the First Interim Analysis of the BLESS Study At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1–80.3%); 22 (55.0%) participants had ...

5. practicalneurology.com practicalneurology.com/news/long-term-real-world-study-results-show-xcopri-is-highly-effective-as-a-treatment-for-reducing-seizures/2470359/

Long-Term, Real-World Study Results Show Xcopri Is Highly ... Long-term treatment with Xcopri (cenobamate tablet; SK Life Sciences, Paramus, NJ) was safe and highly effective in reducing seizure frequency.

6. xcoprihcp.com xcoprihcp.com/safety/

XCOPRI® (cenobamate tablets) CV Safety Discontinuation rates due to adverse reactions were 11% (100 mg), 9% (200 mg), and 21% (400 mg) for patients on XCOPRI compared with 4% for patients on ...

7. sklifescienceinc.com sklifescienceinc.com/pdf/Long_Term_Efficacy_and_Safety_Data_of_XCOPRI%C2%AE_cenobamate_tablets_CV_Published_in_Neurology.pdf

Long-Term Efficacy and Safety Data of XCOPRI® ( ... Results from the study showed the long-term clinical efficacy and safety of cenobamate for adult patients with partial-onset (focal) seizures.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01397968

NCT01397968 | Efficacy and Safety of YKP3089 in ... This study is to evaluate the efficacy of YKP3089 in reducing seizure frequency when compared to baseline in subjects with partial onset seizures not fully ...