Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)
Conditions
Keywords
Drug Therapy
Brief summary
The main aim of the study is to learn if soticlestat, when given as an add-on therapy, reduces the number of seizures in children and adults with Dravet Syndrome (DS) or Lennox-Gastaut Syndrome (LGS). Participants will receive their standard anti-seizure therapy, plus tablets of soticlestat. There will be scheduled visits and follow-up phone calls throughout the study.
Detailed description
The drug being tested in this study is called soticlestat (TAK-935). Soticlestat administered long-term in pediatric and adult participants who participated in an antecedent soticlestat Phase 3 clinical study will be assessed for additional safety and tolerability data along with efficacy analysis, as well as palatability and acceptability of soticlestat in the pediatric population. The study will enroll approximately 400 participants. All participants will receive soticlestat based on their weight in the 2-week Titration Period (for participants who roll over from an antecedent double-blind study). Following the Titration Period, participants will continue to receive the same dose in the Maintenance Period. At the end of maintenance period, the dose will be down-tapered (unless already at the lowest dose) and then stopped. Participants not tolerating minimum dose of 100 mg twice a day (BID) will be discontinued from the study. This multi-center trial will be conducted worldwide. The overall time to participate in the study will be approximately 4 years, or until the study is stopped at the discretion of the sponsor, or the product is approved and launched. Participants who discontinue study drug treatment before the completion of the study, will continue to be followed per protocol and maintain a daily seizure diary until the final follow-up phone call.
Interventions
DRUGSoticlestat
Soticlestat mini-tablets or tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 56 Years
Healthy volunteers
No
Inclusion criteria
1\. Participant must have: * Been previously enrolled in a phase 3 soticlestat clinical study.
Exclusion criteria
1. 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. 2. 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. 3. Participant is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. Participants who have positive answers on item numbers 4 or 5 on the CSSRS before dosing are excluded. This scale will only be administered to participants aged ≥6 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) | Up to end of study (approximately 3.6 years) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it was considered related to the drug. A TEAE was defined as any AE that started or increased in severity after the first dose of the study drug in this open label extension (OLE) study. |
| Number of Participants in Each Category of the Columbia-Suicide Severity Rating Scale (C-SSRS) Over Time | At first visit post-baseline (Visit 1 [V1], Day 1 of the current study), Week 13 (V4), Week 26 (V5), Week 52 (V7), Week 78 (V9), Week104 (v11), Week 130 (V12) and Week 156 (V13) | C-SSRS systematically tracks suicidal ideation and behavior. Responses to questions in the C-SSRS at baseline and each post-baseline time point were collected for participants ≥6 years of age. C-SSRS incidences were categorized as follows: No Suicidal Ideation or Suicidal Behavior or Non-suicidal Self-injurious Behavior (No SI or SB or NSSJB), Non-suicidal Self-injurious Behavior (NSSJB), Suicidal Ideation (SI), and Suicidal Behavior (SB). For each visit (V), the "Yes" answer to the question with the highest severity rank was used to determine the C-SSRS category of a participant. The category Missing indicates the number of participants for whom no data was collected at the particular time point. For each time point only categories with at least 1 participant are presented. BL denotes Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Body Weight for All Age Groups | From Baseline to Week 104 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Change From Baseline in Height for All Age Groups | Baseline to Week 104 | BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories. |
| Number of Participants in Each Tanner Stage for Children 6 to 17 Years of Age During the Study | From Baseline to Week 130 | Tanner assessment scores were used to document the stage of development of puberty by assessing the secondary sexual characteristics, rated in 5 stages: Stage 1 (no development) to 5 (adult-like development in quantity and size) by age (6 to 17 years of age) and sex (boys and girls) during the study. Tanner scale boy clinical classification test names for each stage are reported as follows: TANN02-Genitalia and TANN02-Pubic Hair. Tanner scale girl clinical classification test names for each stage are reported as follows: TANN01-Breast and TANN01-Pubic Hair. |
| Absolute Value for Insulin-like Growth Factor 1 (IGF-1) for Children 2 to 17 Years of Age During the Study | From Baseline to Week 130 | Absolute values of IGF1 were summarized descriptively as a continuous variable by age and by sex (male and female). If multiple assessments for a participant at different visits at a particular age were available, then the average of all data for that participant were used for the summary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Seizure Frequency Per 28 Days | From Baseline to Week 156 | Seizure frequency per 28 days was defined as total number of seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100. |
| Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in DS Cohort | From Baseline to Week 156 | Convulsive seizure frequency per 28 days was defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of convulsive seizures per 28 days during Treatment Period - frequency of convulsive seizures per 28 days at Baseline) divided by the frequency of convulsive seizures per 28 days at Baseline multiplied by 100. |
| Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days in LGS Cohort | From Baseline to Week 144 | MMD seizure frequency per 28 days was defined as the total number of MMD seizures reported during the period divided by the number of days during the period seizures were assessed multiplied by 28. Percent change from baseline was defined as (frequency of MMD seizures per 28 days during the Treatment Period - frequency of MMD seizures per 28 days at Baseline) divided by the frequency of MMD seizures per 28 days at Baseline multiplied by 100. |
| Number of Participants With Improvement in the Clinical Global Impression of Improvement (CGI-I) Score | From Baseline to Week 156 | The CGI-I Clinician is a 7-point Likert scale that the investigator uses to rate a participant's change in overall seizure control, behavior, safety and tolerability, after the initiation of study drug relative to Baseline (before treatment with study drug). The participants were rated as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). Reported here is the number of participants with improvement, which includes the CGI-I responses: very much improved, much improved, minimally improved. |
| Number of Participants With Improvement in the Caregiver Global Impression of Improvement (Care GI-I) Score | From Baseline to Week 156 | The Care GI-I is a 7-point Likert scale that the caregiver used to rate a participant's change in overall seizure control, behavior, safety and tolerability after the initiation of study drug relative to Baseline (before treatment with study drug). The participants were rated as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). The parent/caregiver completed the Care GI-I via interview. Reported here is the number of participants with improvement, which includes the Care GI-I responses: very much improved, much improved, minimally improved. |
| Number of Participants With Improvement in the CGI-I Seizure Intensity and Duration Score | From Baseline to Week 156 | The CGI-I seizure intensity and duration instrument was used by the parent/caregiver to rate a participant's change in intensity and duration of convulsive seizures (DS Cohort) or MMD seizures (LGS Cohort) from Baseline. The participant's symptoms were rated on 7-point scale as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). Reported here is the number of participants with improvement, which includes the CGI-I Seizure responses: very much improved, much improved, minimally improved. |
| Number of Participants With Improvement in CGI-I Nonseizure Symptoms Score | From Baseline to Week 156 | The CGI-I nonseizure symptoms instrument is a series of single-item assessments that the investigator used to rate a participant's change in the caregiver-identified symptoms and impacts in select nonseizure domains since initiating the study drug. The participants were rated on 7-point scale by the investigator as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). At Baseline, a symptoms form was completed by the clinician in collaboration with the primary caregiver to assess the participants status based on the presence of any nonseizure symptoms. Reported here is the number of participants with improvement, which includes the CGI-I nonseizure symptoms responses: very much improved, much improved, minimally improved. |
| Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Score | From Baseline to Week 156 | The QI-Disability tool is a parent/caregiver-reported questionnaire that evaluates quality of life in children with intellectual disabilities. It contains 32 items covering 6 domains of quality of life: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Items were rated on a 5-point Likert scale and then transformed to a scale of 0 to 100. Possible scores range from 0-100, with higher scores indicating better quality of life. Negative change from baseline indicates worsening of quality of life. |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Mexico, Netherlands, Poland, Russia, Serbia, Spain, Ukraine, United States
Contacts
STUDY_DIRECTORMedical Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at various investigative sites globally from 04 March 2022 to 24 September 2025.
Pre-assignment details
A total of 352 participants with Dravet Syndrome (DS) or Lennox-Gastaut Syndrome (LGS) who had participated in phase 3 clinical studies, TAK-935-3001 (NCT04940624), or TAK-935-3002 (NCT04938427), respectively, and who continued to receive standard-of-care (SOC) antiseizure therapy were enrolled in the study for added treatment with soticlestat.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 11.9 years STANDARD_DEVIATION 7.34 |
| Columbia-Suicide Severity Rating Scale (C-SSRS) No SI or SB or NSSJB | 277 Participants |
| Columbia-Suicide Severity Rating Scale (C-SSRS) NSSJB | 0 Participants |
| Columbia-Suicide Severity Rating Scale (C-SSRS) SB | 3 Participants |
| Columbia-Suicide Severity Rating Scale (C-SSRS) SI | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 325 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Height | 137.47 centimeter (cm) STANDARD_DEVIATION 23.813 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 127 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 203 Participants |
| Sex: Female, Male Female | 151 Participants |
| Sex: Female, Male Male | 201 Participants |
| Weight | 36.99 kilogram(kg) STANDARD_DEVIATION 19.544 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 352 |
| other Total, other adverse events | 214 / 352 |
| serious Total, serious adverse events | 86 / 352 |
Outcome results
None listed