~120 spots leftby May 2026

Soticlestat for Dravet Syndrome

Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Takeda
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.
Is soticlestat a promising drug for Dravet Syndrome?Yes, soticlestat is a promising drug for Dravet Syndrome. It has shown good results in reducing seizure frequency and is considered safe, making it a strong option for treating this condition.12567
What safety data is available for Soticlestat in treating Dravet Syndrome?Soticlestat, also known as TAK-935 or OV-935, has been evaluated for safety in several studies. The ELEKTRA study, a phase 2 trial, assessed its safety and efficacy as an adjunctive therapy in children with Dravet Syndrome (DS) or Lennox-Gastaut Syndrome (LGS). A systematic review and network meta-analysis compared Soticlestat with other antiseizure medications, finding it to be effective and relatively safe, with a lower probability of adverse events compared to some other treatments. Overall, Soticlestat is considered a promising and safe adjunctive treatment for DS.34567
What data supports the idea that Soticlestat for Dravet Syndrome (also known as: Soticlestat, TAK-935, OV-935) is an effective treatment?The available research shows that Soticlestat is effective in reducing seizures for patients with Dravet Syndrome. In a study comparing different drugs, Soticlestat was found to be the most likely to reduce seizure frequency by 50% or more compared to the baseline. It was also noted to be safer than some other treatments, like stiripentol and fenfluramine, which are also used for Dravet Syndrome. This suggests that Soticlestat is a promising option for managing seizures in this condition.23567
Do I have to stop taking my current medications for this trial?No, you will not have to stop taking your current medications. Participants will continue their standard anti-seizure therapy and add soticlestat.

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.

Exclusion Criteria

I am not at risk of harming myself or others.

Treatment Details

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.
1Treatment groups
Experimental Treatment
Group I: SoticlestatExperimental Treatment1 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.

Find a clinic near you

Research locations nearbySelect from list below to view details:
University of Iowa Hospitals & Clinics - (CRS)Iowa City, IA
University of ToledoToledo, OH
Seattle Children's HospitalSeattle, WA
MultiCare Institute for Research & Innovation (Tacoma)Tacoma, WA
More Trial Locations
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Who is running the clinical trial?

TakedaLead Sponsor

References

Stiripentol open study in Japanese patients with Dravet syndrome. [2018]To survey the treatment situation of Dravet syndrome in Japan and to compare this result with effectiveness of stiripentol (STP) add-on therapy in an open-label multicenter study.
Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood? [2019]To evaluate continuing stiripentol treatment in adulthood in Dravet syndrome (DS).
Recent Advances in the Drug Treatment of Dravet Syndrome. [2020]Dravet syndrome is a rare but severe epilepsy syndrome that begins in the first year of life with recurrent seizures triggered by fever that are typically prolonged and hemiclonic. The epilepsy is highly drug resistant. Although development is normal at onset, over time, most patients develop moderate-to-severe intellectual disability, behavior disorders, and a characteristic crouch gait. There is a significant mortality, predominantly owing to sudden unexpected death in epilepsy. Complete seizure control is rarely attainable. Initial therapy includes valproic acid and clobazam, but response is typically inadequate. The results of new drugs for Dravet syndrome, including stiripentol, cannabidiol, and fenfluramine, are very promising. Stiripentol was associated with a greater than 50% reduction in convulsive seizure frequency in 71% of cases, when added to valproic acid and clobazam, and also markedly reduced status epilepticus. Pharmaceutical-grade cannabidiol resulted in a median change in monthly motor seizures from baseline of - 36.5%. Fenfluramine was associated with a greater than 50% reduction in seizures of 70%, with one quarter of cases achieving near seizure freedom over the duration of the trial. These agents are generally well tolerated, with few patients discontinuing for adverse effects. There is limited evidence to date regarding improvement in cognition with these newer agents; however, a meaningful change is challenging to assess over short trial periods and requires longer follow-up studies. While current treatments focus predominantly on seizure control, newer therapies including genetic treatments and antisense oligonucleotides can target the SCN1A channelopathy, and thus, may also significantly impact the important co-morbidities associated with this syndrome.
Treatment with brivaracetam in children - The experience of a pediatric epilepsy center. [2020]The new anticonvulsant brivaracetam is a levetiracetam analog which binds to the synaptic vesicle protein 2A, and inhibits excitatory neurotransmitters' release. Brivaracetam was Food and Drug Administration (FDA) and European Medicine Agency (EMA) approved in 2016 as adjunctive treatment for focal onset seizures in patients over 16 years of age, and in 2018 for children over four years of age. Our aim was to describe effectiveness and tolerability in real-life pediatric epilepsy clinic.
A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. [2022]Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its active metabolite norclobazam may increase somnolence, and an interaction with STP and VPA may increase gastrointestinal adverse events. Cannabidiol has a bi-directional interaction with CLB producing an increase in plasma concentrations of 7-OH-CBD and norclobazam resulting in the potential for increased somnolence and sedation. In addition, CBD is associated with elevations of liver transaminases particularly in patients taking concomitant VPA. The interaction between FFA and STP requires a dose reduction of FFA. Furthermore, concomitant administration of VPA with topiramate has been associated with encephalopathy and/or hyperammonaemia. Finally, we briefly describe other ASMs used in Dravet syndrome, and current key clinical trials.
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]Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare treatment-resistant childhood epilepsies classed as developmental and epileptic encephalopathies. ELEKTRA investigated the efficacy and safety of soticlestat (TAK-935) as adjunctive therapy in children with DS or LGS (NCT03650452).
Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis. [2022]Purpose: Recently, the U.S. Food and Drug Administration (FDA) approved stiripentol, cannabidiol, and fenfluramine to treat patients with Dravet syndrome (DS). Moreover, soticlestat was determined as a promising new drug for the treatment of DS as it has good efficacy and safety. However, the efficacy and safety of these drugs have not yet been evaluated in "head-to-head" trials. This study aimed to compare and evaluate the efficacy and safety of these adjunctive antiseizure medications in the treatment of DS. Methods: We searched in PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) and open-label extension (OLE) studies in patients with DS. We performed a random-effect meta-analysis of OLE studies and a network meta-analysis for RCTs to evaluate the efficacy and safety of antiseizure medications in the treatment of DS. Primary efficacy outcomes were defined as a &#8805;50% reduction in seizure frequency compared with baseline. Furthermore, safety evaluation indicators were defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) during treatment. Relative ranking was assessed using the surface under the cumulative ranking curve (SUCRA) probabilities. Results: Seven RCTs involving four antiseizure medications (stiripentol, cannabidiol, fenfluramine, and soticlestat) and a total of 634 patients were included in the analysis. According to the SUCRA results, all four drugs significantly reduced the frequency of seizures compared with the placebo. Soticlestat was the most likely to reduce seizure frequency by &#8805;50% compared to the baseline [risk ratio (RR): 19.32; 95% confidence interval (CI): 1.20-311.40], followed by stiripentol and fenfluramine. Stiripentol was ranked highest for the near percentage reduction in the seizure rate from baseline [RR: 12.33; 95% CI: 1.71-89.17] and the occurrence of any treatment-emergent adverse events [RR: 3.73; 95% CI: 1.65-8.43] and serious adverse events [RR: 4.76; 95% CI: 0.61-37.28]. A total of ten OLE studies containing 1,121 patients were included in our study. According to the results of the meta-analysis, the order of probability of reducing seizure frequency by &#8805;50% was fenfluramine (0.715, 95% CI: 0.621-0.808), stiripentol (0.604, 95% CI: 0.502-0.706), cannabidiol (0.448, 95% CI: 0.403-0.493). And the probability of occurrence of AEs is ranked as fenfluramine(0.832, 95% CI: 0.795-0.869), cannabidiol (0.825, 95% CI:0.701-0.950), stiripentol (0.823, 95% CI: 0.707-0.938), soticlestat (0.688, 95% CI: 0.413-0.890). Conclusion: According to the results of indirect comparison of efficacy and safety, cannabidiol is slightly inferior to the other three antiseizure medications in terms of efficacy and safety. Soticlestat, fenfluramine, and stripentol may have little difference in efficacy, but soticlestat and fenfluramine are safer. Soticlestat is probably the best adjunctive antiseizure medication, followed by fenfluramine. This conclusion is consistent with the comparison of long-term efficacy and safety.