Carisbamate for Lennox-Gastaut Syndrome

Recruiting at 48 trial locations

Overseen By Barbara Remes

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: SK Life Science, Inc.

Must be taking: Anti-seizure medications

Must not be taking: Vigabatrin, Felbamate, CYP3A inducers

Disqualifiers: Progressive neurologic disease, Cardiac disease, Hepatic disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

252 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests carisbamate (also known as Comfyde, YKP 509, or RWJ-333369) to determine its effectiveness in reducing drop seizures in individuals with Lennox-Gastaut Syndrome (LGS), a condition causing various seizures and developmental delays. Participants will receive either carisbamate or a placebo to compare its effectiveness in managing these seizures. The trial seeks individuals who have experienced drop seizures that can lead to falls or injuries and are already on stable doses of 1 to 4 anti-seizure medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial requires that participants have been on a stable dose of 1 to 4 anti-seizure medications for at least 4 weeks before starting. Some medications, like vigabatrin, must be stopped at least 5 months before the trial. If you're taking certain medications like Epidiolex, you may need to adjust your cannabidiol use.

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

Research has shown that carisbamate has been tested for safety and tolerability in people with Lennox-Gastaut Syndrome (LGS). In earlier studies, both adults and children with LGS used carisbamate. These studies aimed to assess reactions to the treatment and its long-term safety.

Most participants tolerated carisbamate well. Common side effects included sleepiness and dizziness, which were usually mild and decreased over time. No major safety issues halted the study or required urgent medical attention.

Carisbamate is still undergoing testing and is not yet approved for general use. However, reaching this phase of clinical testing suggests that earlier trials found it safe enough for further study in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Lennox-Gastaut Syndrome?

Carisbamate is unique because it offers a novel approach to managing Lennox-Gastaut Syndrome, a severe form of epilepsy. Unlike typical treatments like valproate and clobazam, which work by modulating neurotransmitter activity, carisbamate may offer a different mechanism of action that could potentially lead to better control of seizures. Researchers are excited about carisbamate because early studies suggest it might be effective with potentially fewer side effects, providing a new option for patients who don't respond well to current therapies.

What evidence suggests that carisbamate might be an effective treatment for Lennox-Gastaut Syndrome?

Research has shown that carisbamate can greatly reduce seizures in people with Lennox-Gastaut Syndrome (LGS). One study found that patients taking 20 mg/kg of carisbamate daily experienced 41.9% fewer drop seizures. Drop seizures involve a sudden loss of muscle control, often causing falls. This reduction was significant compared to those taking a placebo, which contains no active medicine. In this trial, participants will be assigned to different groups, including those receiving varying doses of carisbamate and those receiving a placebo, to further evaluate its effectiveness in managing seizures in people with LGS. ^{1 3 4 6 7}

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 and adults aged 4-55 with Lennox Gastaut Syndrome (LGS), experiencing multiple seizure types including drop seizures. Participants must have a history of LGS onset before age 11, be on stable anti-seizure medications, and not have progressive neurological diseases or significant other health issues. Women of childbearing potential must use birth control.

Inclusion Criteria

History of COVID-19 vaccination is permitted

I am between 4 and 55 years old.

I am using cannabidiol products that are not Epidiolex.

Exclusion Criteria

You have had a positive test for HIV.

You have had a severe allergic reaction or a serious rash from a medication in the past.

I am scheduled for epilepsy surgery or device insertion during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants undergo titration to determine the appropriate dosage of carisbamate or placebo

2 weeks

Double-blind Treatment

Participants receive either carisbamate or placebo to evaluate efficacy and safety in reducing seizures

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension (optional)

Participants may opt into continuation of treatment long-term with carisbamate

What Are the Treatments Tested in This Trial?

Interventions

• Carisbamate

Trial Overview The study tests the effectiveness of Carisbamate as an additional treatment to reduce drop seizures in those with LGS compared to a placebo. It aims to see if adding Carisbamate helps decrease the frequency of these seizures when taken alongside standard seizure medications.

How Is the Trial Designed?

Group I: Carisbamate 300 mg BID arm Experimental Treatment 1 Intervention

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

Group II: Carisbamate 200 mg BID arm Experimental Treatment 1 Intervention

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

Group III: Placebo matched to 200 mg BID arm Placebo Group 1 Intervention

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

Group IV: Placebo matched to 300 mg BID arm Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

SK Life Science, Inc.

Lead Sponsor

Trials

42

Recruited

8,900+

Published Research Related to This Trial

High-dosage clobazam (1.0 mg/kg/day) showed the strongest treatment effect for Lennox-Gastaut syndrome (LGS) with an effect size of 0.80, indicating a large improvement compared to placebo.

Both high- and medium-dosage clobazam were found to be more effective than other adjunctive treatments for LGS, such as felbamate, lamotrigine, and topiramate, which had low effect sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect comparison of clobazam and other therapies for Lennox-Gastaut syndrome. Cramer, JA., Sapin, C., François, C.[2018]

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that is resistant to many treatments, and it requires a personalized approach to medication based on the specific types of seizures experienced by the patient.

Valproic acid is a first-line treatment for LGS, but other antiepileptic drugs like lamotrigine, rufinamide, and cannabidiol have shown efficacy, with cannabidiol demonstrating strong evidence against LGS seizures, although further long-term studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacological management of Lennox-Gastaut syndrome and critical literature review. Verrotti, A., Striano, P., Iapadre, G., et al.[2018]

A study of 54 children with Lennox-Gastaut syndrome (LGS) revealed that most patients had severe symptoms, including mental retardation in 96% and abnormal EEGs in all, highlighting the complexity of managing this condition.

The most effective treatment combination identified was sodium valproate and lamotrigine, suggesting that tailored multi-drug regimens can significantly improve seizure control and potentially enhance the quality of life for LGS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical characteristics and responsiveness to treatment in Lennox-Gastaut syndrome. A retrospective hospital audit. Habib, HS.[2012]

Lennox-Gastaut syndrome, affecting 3% of children with epilepsy, shows limited efficacy from current medications, with no drug achieving high efficacy for complete seizure control, as highlighted by a Cochrane review.

The ketogenic diet may offer better outcomes than traditional antiepileptic drugs and should be considered early in treatment, emphasizing the need for improved understanding and research into the disorder's underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of Lennox-Gastaut syndrome. Michoulas, A., Farrell, K.[2021]

A case study of a patient with Lennox-Gastaut syndrome (LGS) showed that a combination therapy of levetiracetam, lamotrigine, and valproate successfully controlled all seizure types and resolved abnormal electroencephalographic discharges.

This suggests that logical combination therapy can be an effective treatment option for LGS, even in patients who do not respond to surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Patient with Lennox-Gastaut Syndrome with Combination of Levetiracetam, Lamotrigine and Valproate after Failure of Corpus Callosotomy. Farzi, MA.[2022]

Citations

1. clinicaltrials.eu clinicaltrials.eu/inn/carisbamate/

Carisbamate – Application in Therapy and Current Clinical ... Studies in adults and children with Lennox-Gastaut Syndrome to evaluate its safety and effectiveness in reducing seizures. Trials assessing its efficacy as an ...

2. medicalinfo.sklifescienceinc.com medicalinfo.sklifescienceinc.com/clinical-trials

Clinical Trials Information | SK life science - MedAffairs Search Results : 31 ; Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome (Lennox Gastaut Syndrome), Carisbamate, Completed.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05219617

Study Details | NCT05219617 | Investigate Efficacy and ... To evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the total number of seizures compared with placebo in pediatric and adult ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20549076

Clinical Trials About this study​​ The purpose of this study is to evaluate the effectiveness of carisbamate (YKP509) as adjunctive treatment in reducing the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10480363/

Lennox-Gastaut Syndrome: Current Treatments, Novel ... After 14 weeks of treatment, the 20 mg/kg/day group had a 41.9% reduction in drop seizures (p = 0.005 compared to placebo), 10 mg/kg/day group ...

6. orpha.net orpha.net/en/research-trials/clinical-trial/658097?name=&mode=&country=&recruiting=0&terminated=0

A Randomized, Double-blind, Placebo-Controlled Study to ... A Randomized, Double-blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04062981

Carisbamate Safety Study in Adult and Pediatric Subjects ... Open-label extension study from YKP509C001 to evaluate the safety and tolerability of carisbamate in subjects with Lennox-Gastaut Syndrome (LGS).