Epilepsy, Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS)
Conditions
Keywords
Soticlestat, Drug Therapy
Brief summary
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
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.
Interventions
DRUGSoticlestat
Soticlestat tablets or mini-tablets.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. In the opinion of the investigator, the participant has the potential to benefit from the administration of soticlestat
Exclusion criteria
1. Clinically significant disease, that, in the investigator's opinion, precludes study participation. 2. 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). 3. 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. 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced At Least One Treatment-emergent Adverse Event (AE) | From screening up to end of the study (up to approximately 84 months) | An Adverse Event (AE) was 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 vital sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to this medicinal product. A TEAE is defined as any AE that starts or increases in severity during or after the first dose of study drug. |
| Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS) | Baseline, Week 338 | VABS,3rd edition,Parent Caregiver Form:parent-report questionnaire of adaptive functioning/how is individual's routine behaviour at home \& in community.4 domains(Communication,Daily Living,Social Skills\&Relationships,Problem Behaviors) contained 12 subdomains including items(each scored 0-2).Subdomain scores=sum of item scores within that subdomain.Ranges of subdomain scores are:Communication:Listening\&Understanding(0-78);Talking(0-98);Reading\&Writing(0-76),Daily Living:Caring for Self(0-110);Caring for Home(0-60);Living in Community(0-116),Social Skills\&Relationships:Relating to Others(0-86);Playing\&Using Leisure Time(0-72);Adapting(0-66),Problem Behaviors:Section A(0-26);Section B(0-22),Section C(0-40).For 1st 3 domains,higher subdomain scores=higher adaptive functioning,positive CFB=improvement.For Problem Behaviors,higher subdomain scores=more problem behaviors,negative CFB=improvement(reduction in problem behaviors).No subdomain scores combined to compute any total score. |
| Change From Baseline in Behavior Measures Using Total Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age | Baseline, Week 338 | The ABC-C measures psychiatric symptoms and behavioral disturbance exhibited by individuals across 5 subscales with 58 items: Irritability subscale (15 items); Lethargy/Social Withdrawal subscale (16 items); Stereotypic Behavior subscale (7 items); Hyperactivity subscale (16 items); and Inappropriate Speech subscale (4 items). Each item is rated on a scale of 0 to 3 ("not at all a problem" to "the problem is severe in degree"). The total score was calculated by summing the scores on all 58 items where the total scores ranged from 0 to 174. Higher scores indicate more severity in psychiatric symptoms and behavioral disturbance. Negative change from baseline scores represents improvement. Positive change from baseline scores represents worsening. |
| Change From Baseline in Behavior Measures Using Subscale Scores of the Aberrant Behavior Checklist-Community Edition (ABC-C) for Participants Greater Than Equal to (≥) 6 Years of Age | Baseline, Week 338 | The ABC-C measures psychiatric symptoms and behavioral disturbance exhibited by individuals across 5 subscales with 58 items: Irritability subscale (15 items: Ranges from 0 to 45); Lethargy/Social Withdrawal subscale (16 items: Ranges from 0 to 48); Stereotypic Behavior subscale (7 items: Ranges from 0 to 21); Hyperactivity subscale (16 items: Ranges from 0 to 48); and Inappropriate Speech subscale (4 items: Ranges from 0 to 12). Each item is rated on a scale of 0 to 3 ("not at all a problem" to "the problem is severe in degree"). Subscale scores are calculated as the sum of items within the subscale. Higher subscale scores indicate more severity in psychiatric symptoms and behavioral disturbance. Negative change from baseline score represents improvement. Positive change from baseline score represents worsening. |
| Number of Participants With Changes 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 | Baseline, Week 338 | Suicidal ideation and behavior was assessed in participants with at least 6 years of age using the C-SSRS. The C-SSRS is a 3-part scale that measures suicidal ideation (eg, participants endorses thoughts about a wish to be dead or has other thoughts of suicide), intensity of ideation (frequency), and suicidal behavior (actually, interrupted, and aborted attempts at suicide). SI=Suicidal Ideation; SB=Suicidal Behavior and NSSJB=Non-suicidal Self-injurious Behavior for the categories reported. BL denotes Baseline, V denotes Visit and W denotes Week in the categories. |
| Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline, W denotes Week, HDL denotes High Density Lipid and LDL denotes Low Density Lipid for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells) | Baseline, Week 338 | The percentage of the specified blood cells relative to total leukocyte count was determined and reported. BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Haematology (Liter Per Liter (L/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Haematology (Grams Per Liter (g/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Clinical Laboratory Parameters: Haematology (10^12 Cells Per Liter (10^12/L)) | Baseline, Week 338 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Vital Signs: Blood Pressure | Baseline, Week 338 | BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories. |
| Change From Baseline in Vital Signs: Heart Rate | Baseline, Week 338 | — |
| Change From Baseline in Vital Signs: Respiratory Rate | Baseline, Week 338 | — |
| Change From Baseline in Vital Signs: Temperature | Baseline, Week 338 | — |
| Change From Baseline in Body Weight | Baseline, Week 338 | — |
| Change From Baseline in Electrocardiogram (ECG) Parameters: ECG Heart Rate | Baseline, Week 338 | — |
| Change From Baseline in ECG Parameters: PR Interval | Baseline, Week 338 | — |
| Change From Baseline in ECG Parameters: QRS Duration | Baseline, Week 338 | — |
| Change From Baseline in ECG Parameters: QT Interval | Baseline, Week 338 | — |
| Change From Baseline in ECG Parameters: QTcF Interval | Baseline, Week 338 | — |
| Change From Baseline in ECG Parameters: RR Interval | Baseline, Week 338 | — |
| Number of Participants With Potentially Clinically Significant Clinical Safety Laboratory Test Values | Baseline to Week 338 | ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, HGB: Hemoglobin, ULN: Upper limit of normal, LLN: Lower limit of normal and UREAN: Urea Nitrogen for the specified categories. mmol/L indicates millimoles per liter. Data is reported only for participants who had potentially clinically significant values. |
| Number of Participants With Potentially Clinically Significant Vital Signs | Baseline to Week 338 | Data is reported only for participants who had potentially clinically significant values. |
| Number of Participants With Potentially Clinically Significant Weight and Height | Baseline to Week 338 | The criteria for defining clinical significance for weight category was the participants less than equal to (\<=)10 years of age with weight below minus (-)2standard deviation (SD) of the median weight of the same age and gender per world health organization (WHO) growth chart and for height category was the participants less than (\<)18 years of age with height below -2SD of the median weight of the same age and gender per WHO growth chart. |
| Number of Participants With Potentially Clinically Significant ECG Evaluations | Baseline to Week 338 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in All Seizure 28-day Frequency | Baseline, Week 252 | Change from Baseline is denoted as CFB. |
| Percent Change From Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut Syndrome [LGS] Participants) | Baseline, Week 252 | Change from Baseline is denoted as CFB. |
| Percent Change From Baseline in Convulsive Seizure 28-day Frequency (Dravet Syndrome [DS] Participants) | Baseline, Week 252 | Change from Baseline is denoted as CFB. |
| Percent Change From Baseline in Motor Seizure 28-day Frequency | Baseline, Week 252 | — |
| Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) | Baseline, Week 336 | 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). BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories. |
Countries
Australia, Canada, China, Israel, Poland, Portugal, Spain, United States
Participant flow
Recruitment details
Participants took part in the study at 42 investigative sites globally from 19 July 2018 to 30 July 2025.
Pre-assignment details
Paediatric (ages ≥6 to \<18 years) and adult participants (≥18 years) with developmental and epileptic encephalopathies who participated in antecedent studies of Soticlestat (TAK-935-2001\[NCT03166215\], TAK-935-2002 (ELEKTRA) \[NCT03650452\] and TAK-935-18-002 (ARCADE) \[NCT03694275\]) were enrolled in this open-label extension (OLE) study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 10.4 years STANDARD_DEVIATION 5.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 135 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 44 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 109 Participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 156 |
| other Total, other adverse events | 120 / 156 |
| serious Total, serious adverse events | 43 / 156 |
Outcome results
None listed