LP352 for Epilepsy

Recruiting at 99 trial locations

Overseen By Longboard Study Contact

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Longboard Pharmaceuticals

Must be taking: Antiseizure medications

Must not be taking: Cannabis products

Disqualifiers: Dravet syndrome, Neurodegenerative disorders, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This (DEEp OCEAN Study) is a double-blind, randomized, placebo-controlled, multicenter study to investigate the efficacy, safety, and tolerability of LP352 in the treatment of seizures in children and adults with DEE. The study consists of 3 main phases: Screening, Titration period, Maintenance period, followed by a Taper period and Follow-Up. The total duration of the study will be approximately 24 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a stable dose of 1 to 4 antiseizure medications for at least 4 weeks before the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug LP352 for epilepsy?

The research on similar drugs like levetiracetam and lamotrigine shows they are effective in reducing seizures in both children and adults with epilepsy. Levetiracetam reduced seizure frequency by 50% or more in over half of the patients, and lamotrigine was effective as a single treatment in many children and adolescents, with 42% becoming seizure-free. ^{1 2 3 4 5}

What makes the drug LP352 unique for treating epilepsy?

The drug LP352 is unique for treating epilepsy because it may offer a novel mechanism of action or improved tolerability compared to existing antiepileptic drugs, which often have limitations like poor tolerability and drug interactions. While specific details about LP352 are not provided, it is being studied as a potential alternative to traditional antiseizure medications. ^{4 6 7 8 9}

Eligibility Criteria

This trial is for children and adults with Developmental and Epileptic Encephalopathies (DEE), a group of conditions that include severe forms of epilepsy. Participants must meet specific health criteria to join, but the exact inclusion and exclusion details are not provided here.

Inclusion Criteria

I have been on 1 to 4 seizure medications for at least 4 weeks without changing the dose.

I had seizures start before I was 6, have had different types of seizures, and my development has stalled or reversed.

I was diagnosed with Lennox-Gastaut Syndrome, had seizures before age 8, developmental issues, and specific EEG results.

Exclusion Criteria

I have a brain disorder confirmed by scans or genetic tests.

I have a brain injury or lesion that could cause seizures, not related to my main condition.

I was hospitalized and needed a breathing machine for a severe seizure within the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants are titrated up to the highest tolerated dose of LP352

4 weeks

Visits 2 to 5

Maintenance

Participants maintain the highest tolerated dose of LP352

6 weeks

Visits 5 to 8

Taper

Participants undergo tapering or down titration of LP352

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LP352 (Other)

Trial Overview The study tests LP352, a potential new treatment for seizures in DEE patients. It's compared against a placebo over several phases: Screening, Titration (dose adjustment), Maintenance, Taper period (gradual dose reduction), and Follow-Up, spanning about 24 months.

Participant Groups

Group I: LP352 Experimental Treatment 1 Intervention

Participants will be titrated up to highest tolerated dose of LP352 during the Titration period (Visit 2 - Visit 5), followed by maintenance period (Visit 5 - Visit 8) and then taper/down titration period.

Group II: Placebo Placebo Group 1 Intervention

Placebo for LP352

Who Is Running the Clinical Trial?

Longboard Pharmaceuticals

Lead Sponsor

Trials

5

Recruited

570+

Findings from Research

In a 16-week study involving 1541 patients with treatment-resistant partial seizures, levetiracetam (Keppra) was found to be effective as an add-on therapy, with a median seizure frequency reduction of 50.2% and 15.8% of patients becoming seizure-free.

Levetiracetam was generally well tolerated, with 50.5% of patients reporting mild-to-moderate adverse events like somnolence and dizziness, and only 1.0% experiencing serious adverse events, indicating a favorable safety profile for its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. Steinhoff, BJ., Somerville, ER., Van Paesschen, W., et al.[2018]

Lamotrigine (LTG) has been confirmed as an effective antiepileptic drug through multiple postmarketing studies, demonstrating its broad applications in managing various epilepsy syndromes.

The most serious side effect associated with LTG is skin rash, and specific guidelines have been established for its concurrent use with valproic acid, especially in pediatric patients, to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lamotrigine. Matsuo, F.[2019]

In a study of 102 children with refractory epilepsy, levetiracetam (LEV) as add-on therapy led to a reduction in seizure frequency for 45.1% of participants, with 15.6% becoming seizure-free after at least 6 months of treatment.

LEV was particularly effective for children with partial seizures, achieving a 50% reduction in seizure frequency in 58.3% of those patients, and it was generally well-tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and side effects of levetiracetam on refractory epilepsy in children. Incecik, F., Hergüner, MO., Altunbasak, S.[2021]

Levetiracetam add-on therapy for 65 children with refractory epilepsy showed a significant response rate of 44.8% after 3 months, increasing to 58.6% after 6 months, indicating its efficacy in reducing seizures.

The therapy had a low adverse reaction rate of only 3%, with symptoms primarily involving dysphoria and behavioral issues, suggesting it is a safe option for managing refractory epilepsy in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical efficacy and safety of levetiracetam add-on therapy for child refractory epilepsy. Chen, J., Liu, XM., Yue, X., et al.[2018]

In a study of 72 children and adolescents with epilepsy, lamotrigine (LTG) monotherapy resulted in 42% of patients becoming seizure-free, demonstrating its efficacy in controlling both focal and generalized seizures.

LTG was well-tolerated, with only 6.9% of patients experiencing a rash as an adverse event, and no cases of severe reactions like Stevens-Johnson syndrome, making it a safer option compared to polytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy. Valencia, I., Piñol-Ripoll, G., Khurana, DS., et al.[2018]

A systematic review of 15 randomized controlled trials involving newer antiepileptic drugs (AEDs) showed that these medications are significantly more effective than placebo for adults with partial-onset seizures, with a pooled odds ratio of 2.16 for responder rates.

While newer AEDs demonstrated improved efficacy, they also had a higher incidence of adverse effects, indicating a trade-off between effectiveness and safety that needs to be considered in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of the newer antiepileptic drugs as adjunctive treatment in adults with refractory partial-onset epilepsy: a meta-analysis of randomized placebo-controlled trials. Gao, L., Xia, L., Zhao, FL., et al.[2018]

Levetiracetam (LEV) is a well-tolerated first-line antiseizure medication that shows promising efficacy and minimal drug-drug interactions, making it a valuable option for patients with epilepsy.

The review discusses the development of LEV and its analogs, brivaracetam and padsevonil, which are based on LEV's mechanism of action targeting the synaptic vesicle protein SV2A, highlighting their potential in treating epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. Wu, PP., Cao, BR., Tian, FY., et al.[2023]

In a long-term study involving 217 patients with uncontrolled idiopathic generalized epilepsy, adjunctive levetiracetam (LEV) was effective, with 56.2% of patients achieving seizure freedom for at least 6 months across all seizure types.

LEV was generally well tolerated, with 76% of patients reporting at least one mild to moderate treatment-emergent adverse event, and only 7.8% discontinuing due to side effects, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study. Delanty, N., Jones, J., Tonner, F.[2022]

Lamotrigine (LTG) is recommended as an effective treatment (Level B) for reducing seizure frequency in adults with new-onset focal epilepsy, while levetiracetam (LEV) and zonisamide (ZNS) may also be considered (Level C).

For childhood absence epilepsy, ethosuximide (ETS) or valproic acid (VPA) should be preferred over LTG to decrease seizure frequency, highlighting the importance of selecting appropriate medications based on the type of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Kanner, AM., Ashman, E., Gloss, D., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Lamotrigine. [2019]

3. India pubmed.ncbi.nlm.nih.gov

The efficacy and side effects of levetiracetam on refractory epilepsy in children. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

The clinical efficacy and safety of levetiracetam add-on therapy for child refractory epilepsy. [2018]

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

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of the newer antiepileptic drugs as adjunctive treatment in adults with refractory partial-onset epilepsy: a meta-analysis of randomized placebo-controlled trials. [2018]

7. Singapore pubmed.ncbi.nlm.nih.gov

Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. [2020]