NBI-921352 for Epilepsy

No longer recruiting at 12 trial locations

Overseen By Neurocrine Medical Information Call Center

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Neurocrine Biosciences

Must be taking: Antiseizure medications

Must not be taking: Cannabinoids, systemic steroids

Disqualifiers: Dravet syndrome, head trauma, others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, NBI-921352, to determine its safety and effectiveness in treating seizures for individuals with SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE). Participants will receive either NBI-921352 or a placebo to compare outcomes. The trial targets individuals diagnosed with SCN8A-DEE who experience frequent motor seizures despite using other seizure medications. For those struggling with seizures and who have tried multiple treatments without success, this trial might be suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial does not specify that you need to stop taking your current medications. In fact, you must be on at least one other antiseizure medication to participate. However, you cannot be on systemic steroids or certain cannabinoids unless approved by the Sponsor.

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 be on at least one other antiseizure medication. You cannot take systemic steroids or certain cannabinoids, except Epidiolex, during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NBI-921352 is under study for its safety and effectiveness in treating seizures. Earlier studies have examined its safety and tolerability when combined with other treatments, though detailed safety information remains limited.

As this trial is in Phase 2, the treatment has already passed initial safety tests in earlier studies, suggesting NBI-921352 is reasonably safe for further testing in people. While side effects may still occur, the drug has shown potential to be generally well-tolerated so far.

Prospective participants should discuss any safety concerns with the trial team, who can provide more specific information about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for epilepsy?

NBI-921352 is unique because it offers a new approach to treating epilepsy by targeting specific neural pathways that current medications may not address. Unlike standard treatments like sodium channel blockers, NBI-921352 is designed to modulate neuronal activity more precisely, potentially leading to improved seizure control with fewer side effects. Researchers are excited about this treatment because it represents a novel mechanism of action, which could provide new hope for patients who do not respond well to existing therapies.

What evidence suggests that NBI-921352 might be an effective treatment for epilepsy?

Research has shown that NBI-921352, which participants in this trial may receive, could be a promising treatment for seizures, particularly those linked to the SCN8A gene. In animal studies, this drug successfully stopped seizures in both specially bred and regular mice and rats. It targets a sodium channel called NaV1.6, crucial for controlling nerve signals and potentially reducing seizures. However, a previous study in adults with focal onset seizures did not show a significant reduction in seizures. This indicates that while the drug has potential, further research is needed to fully understand its effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Development Lead

Principal Investigator

Neurocrine Biosciences

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 2 to 21 with SCN8A Developmental and Epileptic Encephalopathy Syndrome. Participants must weigh at least 10 kg, have frequent seizures despite taking up to four antiseizure medications, and not be seizure-free for over 20 days.

Inclusion Criteria

I am currently taking 1 to 4 medications for seizures.

I have at least one noticeable seizure every week and haven't been seizure-free for more than 20 days in a row.

I am between 2 and 21 years old.

Exclusion Criteria

Participated in an interventional clinical trial < 30 days prior to screening

I have symptoms similar to Dravet syndrome.

I have had a serious head injury or disease affecting my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants receive increasing doses of NBI-921352 based on weight

6 weeks

Maintenance

Participants receive treatment at their final tolerated dose

10 weeks

Taper

Participants receive decreasing doses of NBI-921352

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NBI-921352
• Placebo

Trial Overview The study tests NBI-921352 as an additional treatment alongside existing antiseizure medications in patients with SCN8A-DEE. It aims to evaluate the drug's effectiveness in reducing seizures compared to a placebo (a substance with no therapeutic effect).

How Is the Trial Designed?

Group I: NBI-921352 Experimental Treatment 1 Intervention

In the first 6 weeks participants will receive increasing doses of NBI-921352 (Titration Period) based on weight, followed by 10 weeks of treatment at their final tolerated dose (Maintenance Period) and 2 weeks of treatment with decreasing doses (Taper Period).

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo for up to 18 weeks.

Who Is Running the Clinical Trial?

Neurocrine Biosciences

Lead Sponsor

Trials

78

Recruited

6,600+

Kyle W. Gano

Neurocrine Biosciences

Chief Executive Officer since 2024

PhD in Pharmacology

Dr. Sanjay Keswani

Neurocrine Biosciences

Chief Medical Officer

MD

Published Research Related to This Trial

GABA plays a crucial role in controlling neuronal excitability, and many current antiseizure medications enhance GABA transmission, highlighting the need for innovative therapies targeting this system.

Several promising treatments are in development, including repurposed drugs like Staccato® alprazolam for acute seizures and novel therapies like GABAergic interneurons and gene therapies aimed at restoring GABA function, though more clinical data is needed to evaluate their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. Perucca, E., White, HS., Bialer, M.[2023]

Lamotrigine effectively reduces seizure intensity in both bicuculline and pentylenetetrazol models of epilepsy, with significant results observed at higher doses (p < 0.05).

In addition to decreasing seizure intensity, lamotrigine also increases the latency to the first seizure induced by pentylenetetrazol, indicating its potential to delay seizure onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of the effects of lamotrigine on mice using two convulsive tests. Getova, DP., Mihaylova, AS.[2020]

In a long-term study of adjunctive perampanel for patients with refractory partial-onset seizures, over a third of participants remained on the treatment after approximately 4 years, indicating good tolerability and adherence.

The treatment led to a significant reduction in seizure frequency, with a median change of -31.5% from baseline, and no new safety concerns were identified, supporting its long-term efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel Study 207: long-term open-label evaluation in patients with epilepsy. Rektor, I., Krauss, GL., Bar, M., et al.[2021]

Lamotrigine (LTG) was found to have a similar safety profile to placebo in a pooled analysis of four double-blind trials involving 92 patients, with only two patients withdrawing due to adverse effects.

In a larger group of 572 patients from open studies, common side effects included dizziness and headache, but no significant clinical changes or serious adverse events were linked to LTG, indicating it is generally safe when added to existing antiepileptic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human safety of lamotrigine. Betts, T., Goodwin, G., Withers, RM., et al.[2019]

A review of 117 oral generic antiseizure medications (ASMs) in Europe found that 99% of the products assessed met strict bioequivalence criteria, indicating that switching between these generics is unlikely to cause significant changes in drug levels in patients.

However, gabapentin generics showed more variability in bioequivalence and higher intra-subject variability, suggesting that switching between gabapentin generics may carry a greater risk of clinically relevant differences in drug exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence and switchability of generic antiseizure medications (ASMs): A re-appraisal based on analysis of generic ASM products approved in Europe. Odi, R., Franco, V., Perucca, E., et al.[2021]

N-methyl-D-aspartate receptors (NMDARs) are significantly involved in the development of epilepsy, with changes in their activity and expression linked to specific seizure types, as shown in both animal models and clinical studies.

NMDAR antagonists have demonstrated antiepileptic effects in various studies, suggesting they could be a promising treatment option for epilepsy, alongside conventional antiepileptic drugs that may also influence NMDAR function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NMDA receptor complex as a therapeutic target in epilepsy: a review. Ghasemi, M., Schachter, SC.[2022]

Among the 14 new antiepileptic drugs (AEDs) tested, felbamate, gabapentin, lamotrigine, oxcarbazepine, vigabatrin, and zonisamide have shown effectiveness in treating adult localization-related epilepsies, with low toxicity profiles and manageable side effects.

Gabapentin stands out for its lack of liver metabolism and drug interactions, while vigabatrin uniquely increases GABA levels in the CNS, indicating diverse mechanisms of action that may enhance treatment options for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic drugs in development: prospects for the near future. Leppik, IE.[2019]

In a double-blind, placebo-controlled trial involving 34 patients with therapy-resistant epilepsy, lamotrigine as an add-on treatment resulted in a modest and statistically significant reduction in both total and partial seizures compared to placebo.

The treatment was well-tolerated, with only one patient experiencing a rash likely related to lamotrigine, and no significant differences in adverse effects or blood test results between lamotrigine and placebo, indicating low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. Binnie, CD., Debets, RM., Engelsman, M., et al.[2019]

N-methyl-D-aspartate receptors (NMDARs) are crucial in the central nervous system and their abnormal function is linked to seizure disorders and epilepsy, highlighting their importance in understanding these conditions.

NMDAR modulators have demonstrated anticonvulsive effects in both preclinical models and clinical studies, suggesting their potential as effective treatments for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting NMDA Receptor Complex in Management of Epilepsy. Sivakumar, S., Ghasemi, M., Schachter, SC.[2022]

Several new anticonvulsants, including vigabatrin, lamotrigine, and oxcarbazepine, have been developed to address the limitations of conventional treatments, showing promise in improving efficacy and tolerability for epilepsy patients.

These new agents have different mechanisms of action, such as selectively targeting neurotransmission pathways, and while their exact roles in epilepsy management are still being defined, they offer valuable options for improving outcomes, particularly in severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical pharmacology of the new antiepileptic drugs. Perucca, E.[2015]

Using chemogenetic techniques, researchers enhanced the activity of specific inhibitory interneurons in the hippocampus of rodents, showing that this approach can effectively suppress epileptiform activity.

Recruiting parvalbumin (PV) interneurons was particularly effective, leading to over 80% reduction in convulsive behaviors, suggesting that targeted enhancement of inhibitory pathways could be a promising new strategy for treating epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemogenetic Recruitment of Specific Interneurons Suppresses Seizure Activity. Cǎlin, A., Stancu, M., Zagrean, AM., et al.[2022]

Recent studies have highlighted the efficacy and tolerability of various epilepsy treatments, including both new drugs like vigabatrin and established therapies such as lamotrigine and gabapentin, although comparisons between them remain limited.

Encouragingly, new double-blinded placebo-controlled trials are now including children and the elderly, which helps address gaps in research for these often-overlooked patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New antiepileptic drugs and non-pharmacological treatments. Ben-Menachem, E.[2019]

A meta-analysis of 29 trials involving 4,091 patients showed that all six add-on treatments for refractory epilepsy (gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide) were significantly more effective than placebo in reducing seizure frequency by at least 50%.

While there were no definitive differences in efficacy or tolerability among the drugs, topiramate and vigabatrin showed the highest odds of response and discontinuation, indicating they may be the most effective but also potentially the least tolerable options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Marson, AG., Kadir, ZA., Hutton, JL., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8903829/

NBI-921352, a first-in-class, NaV1.6 selective, sodium channel ... Oral administration of NBI-921352 prevented electrically induced seizures in a Scn8a GoF mouse,as well as in wild-type mouse and ratseizure models. NBI-921352 ...

2. elifesciences.org elifesciences.org/articles/72468

NBI-921352, a first-in-class, NaV1.6 selective, sodium ... NBI-921352 was effective in preventing seizures at lower brain and ... Plasma concentration versus efficacy data is shown for the rat ...

3. neurocrine.gcs-web.com neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-provides-development-pipeline-update

Neurocrine Biosciences Provides Development Pipeline Update Phase 2 Proof-of-Concept Study of NBI-921352 in Patients with Focal Onset Seizures Failed to Demonstrate Meaningful Reduction in Seizure ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04873869

Study to Evaluate NBI-921352 as Adjunctive Therapy in ... Treatment response was defined as a ≥50% decrease from baseline in 28-day seizure frequency for countable motor seizures during the treatment period of the ...

5. biospace.com biospace.com/xenon-pharmaceuticals-provides-update-on-partnered-program-with-neurocrine-biosciencesphase-2-proof-of-concept-study-of-nbi-921352-in-patients-with-focal-onset-seizures-failed-to-demonstrate-meaningful-reduction-in-seizure-frequency

Xenon Pharmaceuticals Provides Update on Partnered ... The Phase 2 clinical trial evaluating NBI-921352 in adult patients with focal onset seizures (FOS) failed to demonstrate meaningful reduction in seizure ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05226780

Extension Study to Evaluate How Safe and Tolerable NBI ... Extension study to evaluate how safe and tolerable the drug NBI-921352 is when used as adjunctive therapy in participants with SCN8A developmental and epileptic ...