NBI-921352 for Epilepsy

Recruiting at 11 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

52 Participants Needed

Trial Summary

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.

What data supports the idea that NBI-921352 for Epilepsy is an effective drug?

The available research does not provide specific data on the effectiveness of NBI-921352 for Epilepsy. Instead, it discusses other drugs and treatments for epilepsy, such as lamotrigine, which showed a modest reduction in seizures compared to a placebo in a study. However, there is no direct comparison or data on NBI-921352 in the provided information. ^{1 2 3 4 5}

What safety data is available for NBI-921352 (Zandatrigine) in epilepsy treatment?

The provided research does not contain specific safety data for NBI-921352, also known as Zandatrigine. The studies mentioned focus on other antiepileptic drugs like lamotrigine and perampanel, as well as chemogenetic techniques for seizure suppression. Therefore, no direct safety data for NBI-921352 is available in the given research. ^{5 6 7 8 9}

Is the drug NBI-921352 a promising treatment for epilepsy?

The drug NBI-921352 is considered promising for epilepsy because new antiepileptic drugs are being developed to improve treatment options. These drugs aim to be more effective and have fewer side effects than older ones. Some new drugs target specific brain receptors involved in seizures, which can help control epilepsy better. Overall, the development of new drugs like NBI-921352 offers hope for better management of epilepsy. ^{5 10 11 12 13}

How does the drug NBI-921352 differ from other epilepsy drugs?

NBI-921352 is unique because it may target specific neurotransmitter systems in the brain, potentially offering a new mechanism of action compared to conventional epilepsy drugs, which often have limitations in effectiveness and side effects. ^{5 10 11 12 13}

What is the purpose of this trial?

The objective of this study is to assess the efficacy, safety, and pharmacokinetics of NBI-921352 as adjunctive therapy for seizures in subjects with SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE).

Research Team

Clinical Development Lead

Principal Investigator

Neurocrine Biosciences

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

New antiepileptic drugs and non-pharmacological treatments. [2019]

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

The new antiepileptic drugs: a systematic review of their efficacy and tolerability. [2022]

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

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. [2023]

4. Bulgaria pubmed.ncbi.nlm.nih.gov

A study of the effects of lamotrigine on mice using two convulsive tests. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. [2019]

6. Denmark pubmed.ncbi.nlm.nih.gov

Perampanel Study 207: long-term open-label evaluation in patients with epilepsy. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Chemogenetic Recruitment of Specific Interneurons Suppresses Seizure Activity. [2022]

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

Human safety of lamotrigine. [2019]

9. United States 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. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

11. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting NMDA Receptor Complex in Management of Epilepsy. [2022]

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

The NMDA receptor complex as a therapeutic target in epilepsy: a review. [2022]

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

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