Cenobamate for Epilepsy

(CENOBITE Trial)

Overseen By Jong Woo Lee, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Must be taking: Antiseizure medications

Must not be taking: Phenobarbital, Pentobarbital

Disqualifiers: Medication-related rash, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new epilepsy medication called cenobamate. Researchers aim to evaluate its effectiveness and monitor for serious side effects, such as DRESS syndrome, which can cause skin rashes and fever. Participants will receive the medication under close supervision to ensure safety. This trial may suit individuals with frequent or continuous seizures who are already undergoing EEG monitoring. As an Early Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you continue taking conventional antiseizure medication alongside the trial drug. If you are on medications affecting absorption, like phenobarbital, you may need to stop those.

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

Research has shown that cenobamate may effectively treat epilepsy, particularly for those who haven't succeeded with other treatments. In previous studies, most patients tolerated cenobamate well. For example, one study found that cenobamate reduced seizures without causing serious side effects. However, some patients experienced minor side effects, which are common with many medications.

A key concern with cenobamate is the potential risk of a rare but serious reaction called DRESS syndrome, which can involve a rash, fever, and organ problems. Regular check-ups during treatment help manage this risk.

While researchers continue to study cenobamate, current evidence suggests it is safe for many people. Always consult a healthcare professional about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard epilepsy treatments, which often include medications like levetiracetam, valproic acid, or lamotrigine, cenobamate stands out with its unique mechanism of action. Most treatments work by modulating neurotransmitter levels or blocking sodium channels, but cenobamate targets both sodium channels and GABA receptors, which may help stabilize brain activity more effectively. Researchers are excited because this dual action could potentially bring faster and more significant relief for patients who haven't responded well to existing therapies. Additionally, cenobamate's loading phase and short treatment duration offer a promising option for rapid intervention, a notable advantage over the typical long-term medication regimens.

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

Research shows that cenobamate, which participants in this trial will receive, effectively treats seizures, particularly in people with epilepsy unresponsive to other medications. In previous studies, more than 20% of participants stopped having seizures completely, and over half experienced at least a 50% reduction in seizures. Another study found that patients taking cenobamate had up to twice the reduction in seizures compared to those on a placebo. Long-term evidence supports these results, with nearly 50% of patients experiencing a significant decrease in seizures. These findings suggest that cenobamate could be a promising option for managing epilepsy. ^{2 6 7 8 9}

Who Is on the Research Team?

Jong Woo Lee, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for patients with nervous system disorders, epilepsy, or other neurological conditions who require intensive care. Participants will be closely monitored in a multi-center study involving leading critical care EEG monitoring sites.

Inclusion Criteria

Undergoing EEG monitoring

I experience more than one seizure per hour or have had a long seizure lasting more than 5 minutes.

I am taking medication for seizures.

Exclusion Criteria

History of medication-related rash

I am taking medication that affects how my body absorbs food or drugs.

I cannot take cenobamate due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 400mg load of Cenobamate plus 100mg daily for a maximum of 14 days, with regular monitoring for DRESS syndrome and other adverse reactions

Up to 14 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including seizure cessation and maintenance of therapeutic levels

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cenobamate

Trial Overview

The CENOBITE study tests the drug Cenobamate on a small group of 10 patients to see how it affects those with severe neurological issues. Patients' reactions are tracked using advanced tools like EEG and regular lab tests.

How Is the Trial Designed?

Group I: Cenobamate Experimental Treatment 1 Intervention

400mg load plus 100mg a day for maximum of 14 days

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?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

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 (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, 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]

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40119878/

Real-world effectiveness and tolerability of cenobamate in ...

The primary effectiveness endpoint was the 50% responder rate, defined as the reduction in seizure frequency ≥50%. Results: Data were collected ...

2.

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 ...

3.

seizure-journal.com

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

Efficacy and safety of Cenobamate: a multicenter ...

In the group of patients who had epilepsy surgery in the past, 28 of 47 (59.6 %) had ≥50 % reduction in seizure frequency, including 11 (23.4 %) ...

4.

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, ...

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, Real-World Study Results Show Xcopri Is Highly Effective as a Treatment for Reducing Seizures · 37.3% were 100% responders · 49.2% were ...

6.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK600010/

Clinical Review - Cenobamate (Xcopri) - NCBI - NIH

Despite the availability of several ASMs, there has been no meaningful improvement in epilepsy treatment-related outcomes and no significant increase in seizure ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1059131124001225?dgcid=rss_sd_all

Post-hoc analysis of YKP3089C017 randomized clinical trial

Cenobamate significantly reduced the seizure frequency by 55.6 % compared to 21.5 % with placebo; the percentage of seizure-free patients was 28.3 % in the ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04903314

NCT04903314 | Dose-Escalation Study of Cenobamate ...

The secondary objective of this study is to evaluate the safety and tolerability of cenobamate (YKP3089) following single and multiple dosing. Official ...

9.

pmc.ncbi.nlm.nih.gov

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

Evidence from the First Interim Analysis of the BLESS Study

In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control.