Soticlestat for Dravet Syndrome

Recruiting at115 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Takeda

Must be taking: Anti-seizure therapy

Disqualifiers: Unstable neurologic, psychiatric, cardiovascular, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests soticlestat to reduce seizures in children and adults with Dravet Syndrome or Lennox-Gastaut Syndrome. Soticlestat helps by targeting brain pathways involved in seizure activity. The study will evaluate its safety, effectiveness, and tolerance over time.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants will continue their standard anti-seizure therapy while taking soticlestat.

What data supports the effectiveness of the drug Soticlestat for Dravet Syndrome?

Research shows that Soticlestat significantly reduces seizure frequency in patients with Dravet Syndrome, with a high likelihood of reducing seizures by 50% or more compared to baseline, making it a promising treatment option. ^{1 2 3 4 5}

Is soticlestat safe for humans?

Soticlestat has been studied for safety in children with Dravet syndrome and Lennox-Gastaut syndrome, showing it is generally safe with a lower chance of side effects compared to some other seizure medications. ^{1 2 3 4 6}

How is the drug soticlestat unique in treating Dravet syndrome?

Soticlestat is unique because it has shown promising results in significantly reducing seizure frequency in Dravet syndrome patients, potentially more effectively than other drugs like stiripentol, cannabidiol, and fenfluramine. It is considered a safer option with fewer adverse events compared to some other treatments. ^{1 2 4 5 7}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for children and adults with Dravet Syndrome or Lennox-Gastaut Syndrome who were in a phase 3 soticlestat study. They must not have significant heart rhythm issues, be at risk of suicide, or have other serious health problems that could affect the study.

Inclusion Criteria

Participant must have been previously enrolled in a phase 3 soticlestat clinical study.

Exclusion Criteria

Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, endocrine disease, malignancy including progressive tumors, or other abnormality that may impact the ability to participate in the study or that may potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the medical monitor may be warranted.

Abnormal and clinically significant ECG abnormality at Visit 1 including QT interval with Fridericia correction method (QTcF) >450 milliseconds (ms) confirmed with a repeat ECG using manual measurement of QTcF.

I am not at risk of harming myself or others.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants receive soticlestat titrated from a lower dose to a higher dose based on body weight

2 weeks

Scheduled visits

Maintenance

Participants continue to receive the same dose of soticlestat for long-term safety and tolerability assessment

Approximately 4 years

Scheduled visits and follow-up phone calls

Taper

Dose will be tapered down to a lower dose every 3 days until study drug is discontinued

Up to 1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Final follow-up phone call

Treatment Details

Interventions

• Soticlestat (Other)

Trial Overview The trial tests if adding soticlestat to standard seizure treatments helps reduce seizures in patients with Dravet or Lennox-Gastaut Syndromes. Participants will take soticlestat tablets alongside their usual medication and attend regular visits.

Participant Groups

Group I: Soticlestat Experimental Treatment 1 Intervention

Participants with DS and LGS will receive:Participants weighing \<45kg:Soticlestat,mini-tablets,titrated from lower dose level(60mg to 140mg) to higher dose(100mg to 200mg) twice daily(BID),based on body weight,orally/via enteral feeding tubes including but not limited to nasogastric(NG)-tube,gastrostomy tube(G-tube),MIC-KEY button,upto 2 weeks in Titration Period. Will continue to receive dose they are on at end of Titration Period,for approximately 4 years in Maintenance Period.Dose will be tapered down to lower dose(not less than lowest dose level based on weight)every 3 days until study drug is discontinued(upto 1week) in Taper Period.Participants weighing ≥45kg/adults:Soticlestat mini-tablets/tablets with starting dose of 200mg BID followed by 300mg BID,up to 2 weeks in Titration Period.Will continue to receive 300mg BID for approximately 4 years in Maintenance Period.Dose will be tapered down upto 100mg every 3 days until study drug is discontinued(up to 1 week) in Taper Period.

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]

Dravet syndrome is a severe condition with drug-resistant seizures, and while initial treatments like valproate and clobazam are common, they often fail to control seizures, necessitating the use of adjunct anti-seizure medications (ASMs) such as stiripentol, cannabidiol, and fenfluramine, which have been specifically approved for this syndrome.

Clinicians face challenges with polypharmacy due to potential drug-drug interactions among ASMs, which can affect efficacy and safety; for example, stiripentol can increase the levels of clobazam, leading to increased sedation, while cannabidiol can elevate liver enzymes when used with valproate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. Strzelczyk, A., Schubert-Bast, S.[2022]

New treatments for Dravet syndrome, such as stiripentol, cannabidiol, and fenfluramine, have shown promising results, with stiripentol reducing convulsive seizure frequency by over 50% in 71% of cases when combined with standard medications.

These newer therapies are generally well tolerated with minimal adverse effects, and while they primarily focus on seizure control, there is potential for future treatments to address cognitive and behavioral issues associated with the syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Drug Treatment of Dravet Syndrome. Wirrell, EC., Nabbout, R.[2020]

In a study of 634 patients with Dravet syndrome, soticlestat was found to be the most effective adjunctive antiseizure medication, significantly reducing seizure frequency by over 50% compared to baseline, followed closely by stiripentol and fenfluramine.

While all four medications (soticlestat, stiripentol, fenfluramine, and cannabidiol) reduced seizure frequency compared to placebo, cannabidiol was slightly less effective and had a higher incidence of adverse events, making it the least favorable option among the treatments evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis. Wu, J., Zhang, L., Zhou, X., et al.[2022]

In a study of 40 patients with Dravet syndrome who continued stiripentol treatment from childhood into adulthood, the combination therapy with stiripentol, clobazam, and valproate showed sustained efficacy, with a significant reduction in the frequency and duration of generalized tonic-clonic seizures over time.

While some patients experienced side effects like loss of appetite, these were manageable, and the overall safety profile remained favorable, suggesting that early initiation of stiripentol therapy can lead to better long-term seizure outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood? Chiron, C., Helias, M., Kaminska, A., et al.[2019]

In a study of 31 pediatric patients under 20 years old, brivaracetam was found to be an effective add-on treatment for focal and generalized seizures, with a responder rate of 45.2%.

The medication had minimal side effects, with only mild somnolence, psychosis, and nausea reported, although some patients experienced seizure aggravation, the cause of which remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with brivaracetam in children - The experience of a pediatric epilepsy center. Nissenkorn, A., Tzadok, M., Bar-Yosef, O., et al.[2020]

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

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. [2022]

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

Recent Advances in the Drug Treatment of Dravet Syndrome. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis. [2022]

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

Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood? [2019]

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

Treatment with brivaracetam in children - The experience of a pediatric epilepsy center. [2020]

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

Stiripentol open study in Japanese patients with Dravet syndrome. [2018]