Soticlestat for Rare Epilepsies

(Endymion 1 Trial)

Recruiting at 68 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Must be taking: Anti-seizure medications

Disqualifiers: Pregnancy, Breastfeeding, Suicide risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

156 Participants Needed

Trial Summary

What is the purpose of this trial?

The main aim is to assess the long-term safety and tolerability of soticlestat when used along with other anti-seizure treatment. Participants will receive soticlestat twice a day. Participants will visit the study clinic every 2-6 months throughout the study. Study treatments may continue as long as the participant is receiving benefit from it.

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop your current medications. It aims to assess soticlestat alongside other anti-seizure treatments, so you may be able to continue your current medications.

What data supports the effectiveness of the drug Soticlestat for rare epilepsies?

Research shows that Soticlestat has been studied as an additional treatment for children with Dravet syndrome and Lennox-Gastaut syndrome, which are rare types of epilepsy. In these studies, Soticlestat was found to be safe and showed promise in helping manage these conditions. ^{1 2 3 4 5}

Is soticlestat safe for humans?

Soticlestat has been studied for safety in both healthy adults and children with rare epilepsies. In these studies, it was generally well-tolerated, meaning most people did not experience serious side effects. ^{1 2 3 6 7}

How is the drug Soticlestat different from other drugs for rare epilepsies?

Soticlestat is unique because it targets a specific enzyme involved in the production of certain brain chemicals, which is different from other epilepsy drugs that often focus on altering neurotransmitter activity. This novel approach may offer a new option for patients with rare epilepsies who do not respond well to existing treatments. ^{7 8 9 10 11}

Eligibility Criteria

This trial is for adults and children with rare epilepsies who have previously participated in a soticlestat study. They must not have had serious side effects related to the drug, should be potentially benefiting from it, and cannot be pregnant or breastfeeding. Those with significant diseases or recent suicidal attempts are excluded.

Inclusion Criteria

Participants must have participated in a previous soticlestat study and meet one of the following conditions: Successfully completed a soticlestat clinical study, Received at least 10 weeks of treatment with the study drug in an antecedent placebo-controlled blinded soticlestat clinical study and the participant did not have a serious or severe AE that, in the investigator's or sponsor's opinion, was related to the study drug and would make it unsafe for the participant to continue receiving the study drug, In the opinion of the investigator, the participant has the potential to benefit from the administration of soticlestat

Exclusion Criteria

Suicide attempt within the last year, at significant risk of suicide (either in the opinion of the investigator or defined as 'yes' to suicidal ideation question 4 or 5 on the C-SSRS at Screening) or appearing suicidal per investigator judgment

My doctor thinks my condition makes me unfit for this study.

Participant is currently pregnant or breastfeeding or is planning to become pregnant during the study or within 30 days of the last study drug administration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Optimization

Participants undergo up to 2 weeks of dose optimization depending on the previous study

Up to 2 weeks

Maintenance

Participants receive soticlestat treatment until development is stopped by the sponsor, or the product is approved for marketing, or at any time at the discretion of the sponsor

Long-term

Participants will visit the study clinic every 2-6 months

Safety Follow-up

There will be a 4-week Safety Follow-up Period after the last dose in Maintenance Period, including a 2-week dose Tapering Period

4 weeks

Treatment Details

Interventions

• Soticlestat
• TAK-935

Trial Overview The trial is testing the long-term safety of Soticlestat when taken alongside other anti-seizure medications. Participants will take Soticlestat twice daily and visit the clinic every 2-6 months for as long as they benefit from the treatment.

Participant Groups

Group I: Soticlestat Experimental Treatment 1 Intervention

Treatment: Soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasts until development is stopped by the sponsor, or the product is approved for marketing, or at any time at the discretion of the sponsor.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

In the ELEKTRA study involving 141 children with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), soticlestat treatment led to a significant median reduction in seizure frequency of 30.21% compared to placebo, demonstrating its efficacy as an adjunctive therapy.

The safety profile of soticlestat was comparable to placebo, with most treatment-emergent adverse events being mild or moderate, and no deaths reported, indicating it is a safe option for children with these treatment-resistant epilepsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrome (ELEKTRA). Hahn, CD., Jiang, Y., Villanueva, V., et al.[2023]

Newer antiepileptic drugs developed since the 1990s, such as gabapentin and lamotrigine, offer wider therapeutic benefits, fewer side effects, and reduced drug interactions compared to older medications, making them safer options for treating epilepsy.

These newer drugs not only effectively reduce seizures but also have additional benefits, such as managing chronic neuropathic pain and providing mood stabilization or anti-anxiety effects, highlighting their potential for broader neurological applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Newer antiepileptic drugs]. Matsuura, M.[2007]

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]

References

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

A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrome (ELEKTRA). [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A phase 1b/2a study of soticlestat as adjunctive therapy in participants with developmental and/or epileptic encephalopathies. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and safety assessment of multiple doses of soticlestat in healthy volunteers. [2022]

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

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Adjunctive Treatment With Eslicarbazepine Acetate for Adults and Children With Focal-Onset Epilepsy: A Meta-Analysis. [2022]

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

Eslicarbazepine acetate: an update on efficacy and safety in epilepsy. [2013]

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

Clinical and Electroencephalography Assessment of the Effects of Brivaracetam in the Treatment of Drug-Resistant Focal Epilepsy. [2021]

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

Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies. [2005]

9. Denmark pubmed.ncbi.nlm.nih.gov

Levetiracetam monotherapy for childhood occipital epilepsy of gastaut. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

[Newer antiepileptic drugs]. [2007]

11. 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]