Soticlestat for Dravet Syndrome

No longer recruiting at 142 trial locations

Overseen By Takeda Contact

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must be taking: Anti-seizure therapy

Disqualifiers: Unstable neurologic, psychiatric, cardiovascular, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 whether adding soticlestat to regular anti-seizure medication can reduce seizures in people with Dravet Syndrome or Lennox-Gastaut Syndrome. Participants will continue their usual treatment and take soticlestat tablets as an additional therapy. This trial suits those who have already participated in a Phase 3 soticlestat study and wish to continue treatment. The study process includes regular check-ins and follow-up calls. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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.

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

Research shows that soticlestat is generally well-tolerated by patients. Studies have found its safety profile aligns with past research findings. In trials, most patients did not experience serious side effects, though some reported mild to moderate issues similar to those in earlier studies. Overall, evidence suggests soticlestat is safe to use alongside other treatments for conditions like Dravet Syndrome and Lennox-Gastaut Syndrome. ^{1 2 3 4 5}

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

Soticlestat is unique because it targets a specific enzyme in the brain, known as cholesterol 24-hydroxylase, which plays a role in regulating neuronal excitability. Unlike traditional treatments for Dravet Syndrome, which primarily focus on controlling seizures through broad mechanisms like sodium channel blockers or GABA enhancers, Soticlestat offers a more targeted approach. Researchers are excited about this treatment because it has the potential to reduce seizures more effectively and with potentially fewer side effects, providing a new hope for those with this challenging condition.

What evidence suggests that soticlestat might be an effective treatment for Dravet Syndrome?

Research has shown that soticlestat, the treatment under study in this trial, can help reduce seizures in people with Dravet Syndrome (DS). Studies found that patients with DS who took soticlestat experienced a noticeable decrease in convulsive seizures. While this treatment is also being tested for Lennox-Gastaut Syndrome (LGS) in this trial, the results for DS appear more encouraging. Soticlestat has proven to be safe and well-tolerated by patients, leading to improvements observed by both caregivers and doctors. These findings suggest that soticlestat could be a helpful additional treatment for managing seizures in DS. ^{1 2 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Soticlestat

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 112 patients with Dravet syndrome, only 15% of trials with conventional antiepileptic drugs (AEDs) were effective in reducing seizures by more than 50%, highlighting the challenges in managing this condition.

In contrast, stiripentol (STP) add-on therapy resulted in over 50% reduction in generalized tonic-clonic seizures (GTCS) for 61% of patients, with some achieving seizure freedom, indicating its potential as a beneficial treatment option for Dravet syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stiripentol open study in Japanese patients with Dravet syndrome. Inoue, Y., Ohtsuka, Y., Oguni, H., et al.[2018]

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]

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]

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 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]

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]

Citations

1. aesnet.org aesnet.org/abstractslisting/soticlestat-as-adjunctive-therapy-in-children-and-young-adults-with-dravet-syndrome-the-phase-3-skyline-clinical-trial

soticlestat as adjunctive therapy in children and young adults ... SKYLINE evaluated the efficacy, safety, and tolerability of soticlestat as adjunctive therapy in children and young adults diagnosed with DS.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06422377

A Study Evaluating Soticlestat in Participants With Dravet ... The purpose of this study is to check how soticlestat impacts symptoms of Dravet syndrome [DS] and Lennox-Gastaut syndrome [LGS] in participants who have been ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12055774/

Efficacy, safety, and tolerability of soticlestat (TAK-935) as ... Soticlestat showed significantly higher efficacy in reducing convulsive seizures in patients with DS. Nonetheless, for patients with LGS, the difference ...

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

Takeda Announces Phase 3 Topline Results for Soticlestat Among the six key secondary endpoints, soticlestat showed clinically meaningful and nominally significant results in the responder rate, ...

5. neurologylive.com neurologylive.com/view/soticlestat-improves-caregiver-clinical-measures-endymion-2-trial-dravet-syndrome-lgs

Soticlestat Improves Caregiver and Clinical Measures in ... Soticlestat (Takeda) was safe in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), with treated patients showing improvements in Caregiver ...

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

A phase 2, randomized, double-blind, placebo-controlled ... Drop seizure frequency showed a nonstatistically significant numerical reduction in children with LGS. Soticlestat had a safety profile consistent with previous ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04940624

NCT04940624 | A Study of Soticlestat as an Add-on ... The main aim of the study is to learn if soticlestat, when given as an add-on therapy, reduces the number of convulsive seizures in children and young ...