Soticlestat for Rare Epilepsies

(Endymion 1 Trial)

No longer recruiting at 72 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of soticlestat, a new medication that may help people with rare types of epilepsy manage seizures alongside their current treatments. Participants will take soticlestat tablets twice daily and visit the study clinic every 2-6 months. The trial suits those who have previously participated in a soticlestat study and might benefit from continuing the medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that soticlestat is likely to be safe for humans?

Research has shown that soticlestat is generally safe for people with rare forms of epilepsy. In studies like SKYLINE and SKYWAY, the safety profile of soticlestat matched findings from earlier research, indicating that most participants did not experience serious side effects. Used alongside other seizure medications, soticlestat led to fewer seizures over time. Although the treatment remains under study, these consistent safety results offer encouragement for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for rare epilepsies work by stabilizing electrical activity in the brain or managing neurotransmitters. However, Soticlestat stands out because it targets an enzyme called cholesterol 24-hydroxylase, which plays a role in the cholesterol metabolism in the brain. This new approach aims to reduce the frequency and severity of seizures by addressing a different pathway than current drugs. Researchers are excited about Soticlestat because it offers a novel mechanism that could potentially improve outcomes for patients who don't respond well to existing medications.

What evidence suggests that soticlestat might be an effective treatment for rare epilepsies?

Research has shown that soticlestat, the treatment under study in this trial, may help reduce seizures in people with certain rare types of epilepsy. In one study, patients taking soticlestat experienced a significant decrease in seizure frequency compared to those who did not take it. Specifically, one group saw a 20.6% reduction in drop seizures. Another study found a noticeable decrease in motor seizures, with some patients experiencing up to a 23.6% reduction. These results suggest that soticlestat could effectively manage seizures in people with these challenging conditions. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. takeda.com takeda.com/newsroom/newsreleases/2024/soticlestat-drevat-syndrom-phase3-results/

Takeda Announces Phase 3 Topline Results for Soticlestat Soticlestat narrowly missed the primary endpoint of reduction from baseline in convulsive seizure frequency as compared to placebo (p-value = ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35841234/

A phase 2, randomized, double-blind, placebo-controlled ... Soticlestat treatment resulted in statistically significant, clinically meaningful reductions from baseline in median seizure frequency (combined patient ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03635073

NCT03635073 | A Study of Soticlestat in Adults and ... This global, open-label extension (OLE) study will assess the long-term safety and tolerability of soticlestat in participants with developmental and epileptic ...

4. investors.ovidrx.com investors.ovidrx.com/news/news-details/2020/Phase-2-ELEKTRA-Study-of-Soticlestat-TAK-935OV935-Meets-Primary-Endpoint-Reducing-Seizure-Frequency-in-Children-with-Dravet-Syndrome-or-Lennox-Gastaut-Syndrome-08-25-2020/default.aspx

Phase 2 ELEKTRA Study of Soticlestat (TAK-935/OV935) ... In the ELEKTRA LGS cohort (n=88), patients treated with soticlestat demonstrated a 20.6% median reduction in drop seizure frequency compared to ...

5. neurology.org neurology.org/doi/10.1212/WNL.96.15_supplement.4096

Efficacy, Safety and Tolerability of Soticlestat (TAK-935/ ... Primary outcome results showed median percent seizure frequency of +11.7% (Dup15q cohort) and −23.6% (CDD cohort) from baseline in motor seizure ...

6. investors.ovidrx.com investors.ovidrx.com/news/news-details/2019/Ovid-Therapeutics-Announces-Positive-Initial-Data-from-Ongoing-ENDYMION-Open-Label-Extension-Trial-of-Soticlestat-in-People-with-Rare-Epilepsies-09-23-2019/default.aspx

News Details Ovid Therapeutics Announces Positive Initial Data from Ongoing ENDYMION Open-Label Extension Trial of Soticlestat in People with Rare Epilepsies.