Carisbamate for Lennox-Gastaut Syndrome

Recruiting at 40 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

Trial Summary

What is the purpose of this trial?

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

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.

How does the drug Carisbamate differ from other drugs for Lennox-Gastaut syndrome?

Carisbamate is unique because it is being explored as a potential treatment for Lennox-Gastaut syndrome, a condition with limited effective options, and it may offer a new mechanism of action compared to existing drugs. While other drugs like valproate, lamotrigine, and topiramate are commonly used, Carisbamate's specific effects and benefits for this syndrome are still under investigation, potentially providing a novel approach to managing seizures. ^{1 2 3 4 5}

Research Team

Marc Kamin, MD

Principal Investigator

SK Life Science, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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 (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]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Indirect comparison of clobazam and other therapies for Lennox-Gastaut syndrome. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Medical management of Lennox-Gastaut syndrome. [2021]

3. Korea (South) 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. [2022]

4. Saudi Arabia pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

The pharmacological management of Lennox-Gastaut syndrome and critical literature review. [2018]