SPN-817 for Focal Seizures

Overseen By Supernus Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Supernus Pharmaceuticals, Inc.

Must be taking: ASMs

Must not be taking: Cholinergics, Anticholinergics

Disqualifiers: Generalized epilepsy, Status epilepticus, others

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

Compensation: Varies

Number of Visits: 3

258 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of 1 to 4 current anti-seizure medications (ASMs) for at least 28 days before screening and throughout the study. If you are following a diet plan with your medication, it should also remain stable during the study.

What data supports the effectiveness of the drug SPN-817 for focal seizures?

Research on a similar drug, perampanel, shows it can help reduce seizures in people with focal epilepsy. In some studies, more than half of the patients experienced a significant reduction in seizure frequency. ^{1 2 3 4 5}

How does the drug SPN-817 for focal seizures differ from other treatments?

SPN-817 is unique because it targets specific sodium channel mutations associated with epilepsy, potentially offering a more personalized treatment approach compared to standard anti-seizure medications that do not specifically address these genetic factors. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a Phase 2 double-blind, randomized, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy, safety, and tolerability of SPN-817 in adults with focal onset seizures.

Research Team

Himanshu Upadhyaya, MBBS, MS, MBA

Principal Investigator

Supernus Pharmaceuticals, Inc.

Eligibility Criteria

Adults with focal onset seizures, which are seizures that start in just one part of the brain. Participants must meet certain health standards to be included but specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

My epilepsy does not respond to treatment, as confirmed by the ESCI.

Has a body mass index (BMI) between 18.0 and 40.0 kg/m2

At least 4 clinically observable focal onset seizures accepted by the ESCI prior to the first dose of SM (during the days of baseline Seizure eDiary data collection) and no more than a consecutive 21-day period that was seizure free. To be eligible for the study, participants must comply with the eDiary on at least 90% of the days of baseline data collection

Exclusion Criteria

I have been diagnosed with a complex epilepsy syndrome confirmed by EEG.

I have taken huperzine A in the last 6 months.

My seizures are hard to notice or count.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

1 visit (in-person)

Titration

Participants are titrated to the target dose of SPN-817 or placebo, with prophylactic ondansetron for the first 5 weeks

8-10 weeks

Weekly visits (in-person)

Maintenance

Participants maintain the target dose of SPN-817 or placebo

14 weeks

Bi-weekly visits (in-person)

Tapering

Participants taper off the study medication if not enrolling in the open-label extension

up to 4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 safety phone call

Treatment Details

Interventions

• SPN-817

Trial Overview The trial is testing SPN-817 against a placebo to see if it's effective and safe for treating focal onset seizures. Patients will be randomly assigned to either the drug or placebo group without knowing which they're receiving.

Participant Groups

Group I: SPN-817 Experimental Treatment 1 Intervention

SPN-817, bid

Group II: Placebo Placebo Group 1 Intervention

Placebo, bid

Who Is Running the Clinical Trial?

Supernus Pharmaceuticals, Inc.

Lead Sponsor

Trials

49

Recruited

14,000+

Findings from Research

In a study of 73 patients with untreated focal-onset seizures, 46 patients achieved seizure freedom while on a 4 mg/day dose of perampanel, indicating that continued treatment beyond initial titration can be beneficial.

The analysis showed that 80.4% of responders were early responders with a complete reduction in seizure frequency, while safety outcomes remained consistent across different responder statuses, suggesting no new safety concerns with continued treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience of perampanel monotherapy beyond initial titration to achieve seizure freedom in patients with focal-onset seizures with newly diagnosed or currently untreated recurrent epilepsy: A post hoc analysis of the open-label Study 342 (FREEDOM). Husni, RE., Ngo, LY., Senokuchi, H., et al.[2022]

In a study of 46 patients aged 12 to 63 years with focal epilepsy, perampanel (PER) as an add-on treatment led to a significant reduction in seizure frequency, with 46.5% of patients experiencing a decrease of over 50% in seizures and 25.6% achieving complete seizure cessation.

While 28.2% of patients reported adverse effects, including aggressiveness and sleepiness, the majority (71.7%) experienced an improvement in their quality of life, indicating that PER is generally well-tolerated and effective for managing focal epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perampanel in pharmacotherapy of focal epilepsy: the efficacy and tolerability in routine clinical practice]. Zhidkova, IA., Karlov, VA., Vlasov, PN.[2021]

Zonisamide (ZNS) as an adjunctive therapy for focal epilepsy was effective in reducing seizures by more than 50% in 8 out of 12 patients, indicating its efficacy in managing this condition.

Importantly, ZNS did not negatively impact sleep quality or increase daytime sleepiness, suggesting it is a safe option for patients who may be sensitive to the sleep-related side effects of other antiepileptic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study. Romigi, A., Izzi, F., Placidi, F., et al.[2018]

In a study of 70 Chinese patients with focal-onset seizures, perampanel monotherapy demonstrated a 6-month seizure-freedom rate of 69.84% and a 12-month rate of 65.08%, indicating its efficacy in managing seizures over time.

The treatment was generally safe, with 37.1% of patients experiencing adverse events, primarily dizziness, and only 5.7% withdrawing due to these events, suggesting that perampanel is a viable option for patients aged 4 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: A single-center, prospective, real-world observational study. Ma, H., Zhu, H., Chen, F., et al.[2023]

In a multi-center study of people with epilepsy who had undergone surgery or vagus nerve stimulation, perampanel was found to reduce seizure frequency by at least 50% in 52.8% of patients post-resection, compared to only 16.9% in the VNS group, indicating its effectiveness especially after surgical interventions.

Higher doses of perampanel (greater than 8 mg) were associated with better seizure response and were well tolerated, suggesting that increasing the dose may enhance treatment outcomes for patients with drug-resistant epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the effectiveness of perampanel in people with epilepsy who have previously undergone resective surgery and/or implantation of a vagal nerve stimulator. Davis Jones, G., Stavropoulos, I., Ibrahim, K., et al.[2021]

Pathogenic variants in voltage-gated sodium channel genes (like SCN1A and SCN2A) are linked to various epilepsy types and neurodevelopmental disorders, highlighting their importance in understanding these conditions.

Next generation sequencing has improved the diagnosis of these channelopathies, enabling more precise treatment strategies based on whether the genetic variant causes loss-of-function or gain-of-function in the sodium channels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in treatment of epilepsy-related sodium channelopathies. Musto, E., Gardella, E., Møller, RS.[2020]

Voltage-gated sodium channels (VGSCs), particularly the SCN1A subunit, are crucial for normal brain function and are linked to various epilepsy syndromes, with over 650 genetic variants identified that can lead to severe forms of epilepsy.

Current research methods, including in vitro, in vivo, and in silico approaches, are being developed to better understand the functional impact of these mutations on channel activity and their association with disease severity, but challenges remain in correlating genetic data with clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium channels and the neurobiology of epilepsy. Oliva, M., Berkovic, SF., Petrou, S.[2013]

In a study using N1417H-Scn1a mutant rats, which model human generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI), potassium bromide (KBr) and diazepam (DZP) were found to significantly reduce seizure durations during hyperthermia-induced seizures.

While KBr showed strong anticonvulsant effects similar to DZP, it did not impair motor coordination, unlike DZP, which suggests that KBr may be a safer option for managing seizures in these models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for hyperthermia-induced seizures in Scn1a mutant rats. Hayashi, K., Ueshima, S., Ouchida, M., et al.[2012]

The study found that the SCN1A rs3812718 polymorphism is significantly associated with generalized epilepsy with febrile seizures plus (GEFS+), indicating that individuals with the TT genotype or T allele have a higher risk of developing this condition.

In a comparison of 50 patients with GEFS+ and 50 healthy controls, those with the CT or TT genotypes had a notably increased risk of GEFS+, with odds ratios indicating a strong association, particularly for the TT genotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Association between SCN1A rs3812718 polymorphism and generalized epilepsy with febrile seizures plus]. Ma, QL., Wang, B., Chen, GF., et al.[2020]

The SCN8A gene mutation p.Arg1872Trp leads to severe epilepsy and developmental issues, with studies in mice showing that activating this mutation in excitatory neurons causes convulsive seizures and early death, highlighting the critical role of these neurons in the condition.

Treatment with the sodium channel modulator GS967/Prax330 improved survival in mice with the mutation, suggesting that targeting excitatory neurons may be a promising therapeutic strategy for managing SCN8A encephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SCN8A: When Neurons Are So Excited, They Just Can't Hide It. Gertler, TS., Carvill, GL.[2020]

References

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

Experience of perampanel monotherapy beyond initial titration to achieve seizure freedom in patients with focal-onset seizures with newly diagnosed or currently untreated recurrent epilepsy: A post hoc analysis of the open-label Study 342 (FREEDOM). [2022]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Perampanel in pharmacotherapy of focal epilepsy: the efficacy and tolerability in routine clinical practice]. [2021]

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

Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study. [2018]

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

Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: A single-center, prospective, real-world observational study. [2023]

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

An evaluation of the effectiveness of perampanel in people with epilepsy who have previously undergone resective surgery and/or implantation of a vagal nerve stimulator. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Recent advances in treatment of epilepsy-related sodium channelopathies. [2020]

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

Sodium channels and the neurobiology of epilepsy. [2013]

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

Therapy for hyperthermia-induced seizures in Scn1a mutant rats. [2012]

9. China pubmed.ncbi.nlm.nih.gov

[Association between SCN1A rs3812718 polymorphism and generalized epilepsy with febrile seizures plus]. [2020]

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

SCN8A: When Neurons Are So Excited, They Just Can't Hide It. [2020]