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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SPN-817 for individuals with focal seizures, a type of epilepsy where seizures begin in a specific part of the brain. The goal is to determine if SPN-817 is safe and effective in reducing the frequency and severity of these seizures. Participants will receive either SPN-817 or a placebo (inactive substance) for comparison. Ideal candidates have focal epilepsy resistant to current treatments and experience frequent, noticeable seizures. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that SPN-817 is likely to be safe for humans?

Research has shown that SPN-817, a treatment for focal seizures, has promising safety results from earlier studies. Most participants in these studies tolerated SPN-817 well. For instance, in one long-term study, patients taking SPN-817 experienced a noticeable decrease in the number of seizures over time. This suggests that the treatment is not only effective but also safe for long-term use. Another study on safety found that adults aged 18 to 70 could use SPN-817 without major side effects. While the treatment is still being tested, these earlier findings offer reassurance about its safety for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for focal seizures, which usually include medications like carbamazepine or lamotrigine, SPN-817 offers a unique approach. Researchers are excited about SPN-817 because it utilizes a novel mechanism that targets different pathways in the brain, potentially offering relief for patients who do not respond well to existing medications. This innovative approach could mean fewer side effects and improved seizure control, making SPN-817 a promising candidate for advancing epilepsy treatment.

What evidence suggests that SPN-817 might be an effective treatment for focal seizures?

Research has shown that SPN-817, which participants in this trial may receive, may help reduce focal seizures. In one study, participants experienced a 54.5% reduction in seizures over 28 days. Another report found an average reduction of 58% in seizures. Long-term results are also promising; some patients experienced a 71% reduction after 15 months and a 90% reduction after 32 months. These findings suggest that SPN-817 could effectively manage focal seizures. ^{1 3 4 5 6}

Who Is on the Research Team?

Himanshu Upadhyaya, MBBS, MS, MBA

Principal Investigator

Supernus Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07141329

NCT07141329 | SPN-817 Open-Label Extension Study in ... Greater than or equal to 50% reduction in 28-day frequency of focal seizures during the 1-year Treatment Period relative to baseline. Baseline ...

2. aesnet.org aesnet.org/abstractslisting/the-renaissance-study-interim-results-of-a-phase-2-study-of-spn-817-in-adults-with-treatment-resistant-epilepsy

interim results of a phase 2 study of spn-817 in adults with ... For subjects in the maintenance period, median 28-day seizure frequency was reduced by 54.5% (n=19), with 81.3%, 62.5% and 18.8% experiencing ...

3. ir.supernus.com ir.supernus.com/news-releases/news-release-details/supernus-announces-promising-interim-data-ongoing-open-label

News Release Details Supernus Announces Promising Interim Data from Ongoing Open-Label Phase 2a Study of SPN-817 in Epilepsy · 58% median seizure reduction in the ...

4. neurology.org neurology.org/doi/10.1212/WNL.98.18_supplement.1388

An Open-Label Pilot Trial Assessing the Safety and ... During the long-term SPN-817 maintenance period, the mean reduction in 28-day seizure rate was 71% after 15 months (N=3) and 90% after 32 months ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05518578

Safety and Tolerability Study of SPN-817 in Adult Patients ... This is a multicenter, three-phase, long-term open-label study assessing the safety and tolerability of SPN-817 in adults 18-70 years of age with treatment ...

6. ir.supernus.com ir.supernus.com/static-files/8d19152f-077b-4bde-9280-586d6f702da9

SPN-817 Phase 2a Study ... SPN-817 suggests that it can be: A highly differentiated anti-seizure product for focal seizures. • Overall strong efficacy. • High responder ...