A Study of Soticlestat in Adults and Children With Rare Epilepsies

Study Overview
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Brief Summary
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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.

Detailed Description
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The drug being tested in this study is called soticlestat (TAK-935). This global, open-label extension (OLE) study will assess the long-term safety and tolerability of soticlestat in participants with developmental and epileptic encephalopathy (DEE) who participated in previous short-term efficacy/safety studies of soticlestat. All participants will receive Soticlestat treatment. Participants who rollover from previous blinded study will undergo up to 2 weeks of Dose Optimization Period (depending on the previous study) followed by Maintenance Period. Participants who rollover from an open-label study will continue on their current dose until development is stopped by the sponsor, or the product is approved for marketing, or at any time at the discretion of the sponsor. There will be a 4-week Safety Follow-up Period after the last dose in Maintenance Period, including a 2-week dose Tapering Period.

Official Title
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A Phase 2, Prospective, Interventional, Open-Label, Multi-Site, Extension Study to Assess the Long-Term Safety and Tolerability of Soticlestat (TAK-935) as Adjunctive Therapy in Subjects With Developmental Epileptic Encephalopathies Including Dravet Syndrome, Lennox Gastaut Syndrome, CDKL5 Deficiency Disorder, and Chromosome 15 Duplication Syndrome (ENDYMION 1)

Conditions
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Epilepsy, Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS)

Intervention / Treatment
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* Drug: Soticlestat


Participation Criteria
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Eligibility Criteria
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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: Clinically significant disease, that, in the investigator's opinion, precludes study participation. Enrollment in any other clinical trial involving an investigational drug, device, or treatment in the past 90 days (with the exception of an antecedent study involving Soticlestat). 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. 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.

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soticlestat<br>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. | Drug: Soticlestat<br>* Soticlestat tablets or mini-tablets.<br>* Other names: TAK-935;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experience At least one Adverse Event (AE) | An Adverse Event (AE) is defined any untoward medical occurrence in a subject or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (for example, an abnormal laboratory finding, vital sign or ECG evaluation), symptom, or disease temporally associated with the use of a medicinal product, whether considered related to this medicinal product. | Up to 6 years | 
| Change from Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) | The VABS, 3rd edition, Parent Caregiver Form (VABS-3 Parent Caregiver Form), is a parent-report questionnaire of adaptive functioning or how an individual behaves in their day-to-day life at home and in the community. | Up to 6 years | 
| Change from Baseline in Behavior Measures Using Total Scores and Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants ≥6 Years of age |  | Up to 6 years | 
| Change from Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1,2,3,4, and 5 for Participants ≥6 Years of age |  | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in all Seizure 28-day Frequency |  | Up to 6 years | 
| Percent Change from Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut syndrome [LGS] Participants) |  | Up to 6 years | 
| Percent Change from Baseline in Convulsive Seizure 28-day Frequency (Dravet syndrome [DS] Participants) |  | Up to 6 years | 
| Percent Change from Baseline in Motor Seizure 28-day Frequency |  | Up to 6 years | 
| Change from Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) | CGI-S is used to obtain an assessment of symptom severity, focusing on clinicians' observations of the subject's current cognitive, functional, and behavioral performance. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (among the most severely ill participants). | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soticlestat, Drug Therapy