A Study of Soticlestat in Adults and Children With Rare Epilepsies (Endymion 1)

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)

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.

Study Overview

• Status: Terminated
• Conditions: Epilepsy; Dravet Syndrome (DS); Lennox-Gastaut Syndrome (LGS)
• Intervention / Treatment: Drug: Soticlestat

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.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children's Hospital
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Heidelberg West, Victoria, Australia, 3081
      • Austin Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• China
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 100069
    • Beijing Children's Hospital,Capital Medical University
  • Beijing, China, 100045
    • Beijing Children's Hospital,Capital Medical University
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Changsha, China, 410008
    • Xiangya Hospital of Central South University
  • Guangdong
    • Shenzhen, Guangdong, China, 518026
      • Shenzhen Children's Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University
• Israel
  • Beersheba, Israel, 84101
    • Soroka University Medical Centre
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Holon, Israel, 58100
    • Edith Wolfson Medical Center
  • Petah Tikva, Israel, 49100
    • Schneider Children's Medical Center of Israel - Petah Tikvah - PIN
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center - PPDS
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center - PPDS
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center PPDS
  • Tel Aviv
    • Tel Aviv, Tel Aviv, Israel, 64239
      • Tel Aviv Sourasky Medical Center PPDS
• Poland
  • Krakow, Poland, 30-363
    • Centrum Medyczne Plejady
  • Warsaw, Poland, 02-091
    • Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-355
      • Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne
  • Świętokrzyskie Voivodeship
    • Kielce, Świętokrzyskie Voivodeship, Poland, 25-316
      • NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
• Portugal
  • Lisbon, Portugal, 1169-045
    • Centro Hospitalar Lisboa Central- Hospital Dona Estefania
  • Lisbon, Portugal, 1600-035
    • Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
  • Lisbon, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
• Spain
  • Granada, Spain, 18008
    • Hospital Vithas La Salud
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional (Grupo Quironsalud)
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Madrid, Communidad Delaware
    • Madrid, Madrid, Communidad Delaware, Spain, 28034
      • Hospital Ruber Internacional (Grupo Quironsalud)
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad Navarra
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenosciences Inc
  • California
    • Los Angeles, California, United States, 900095-1752
      • David Geffen School of Medicine at UCLA
    • Los Angeles, California, United States, 90095-8358
      • David Geffen School of Medicine at UCLA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Children's Hospital
    • Aurora, Colorado, United States, 80045-7106
      • Colorado Children's Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Miami, Florida, United States, 33155-3009
      • Nicklaus Children's Hospital
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center Inc
    • Port Charlotte, Florida, United States, 33980
      • Medsol Clinical Research Center Inc
    • Tampa, Florida, United States, 33606
      • University of South Florida
    • Winter Park, Florida, United States, 32789
      • Pediatric Neurology PA
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
    • Atlanta, Georgia, United States, 30322
      • Rare Disease Research, LLC
    • Norcross, Georgia, United States, 30093
      • Center for Rare Neurological Diseases
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H Lurie Childrens Hospital of Chicago
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Epilepsy Research LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - PIN
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Epilepsy Group PA
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Max Benzaquen, M.D., PC
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-1974
      • Northeast Regional Epilepsy Group
    • New Brunswick, New Jersey, United States, 08901
      • Children's Hospital at Saint Peter's University Hospital
  • New York
    • New York, New York, United States, 10016
      • NYU - Ambulatory Care Center (ACC)
    • New York, New York, United States, 10032
      • Columbia University Medical Center - PIN
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center - PPDS
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina Childrens Hospital - PIN
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Jane and John Justin Neurosciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Soticlestat; Participants received soticlestat, tablets orally twice daily at optimized dose, titrated in up to 2 weeks of Dose Optimization Period, followed by Maintenance Period, which lasted until development was stopped by the sponsor, or the product was approved for marketing, or at any time at the discretion of the sponsor.	Drug: Soticlestat; Soticlestat tablets or mini-tablets.; Other Names: TAK-935

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced At Least One Treatment-emergent Adverse Event (AE)	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.	From screening up to end of the study (up to approximately 84 months)
Change From Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS)	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.	Baseline, Week 338
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	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.	Baseline, Week 338
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	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.	Baseline, Week 338
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	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.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Grams Per Liter (g/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Units Per Liter (U/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Micromoles Per Liter (µmol/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Serum Chemistry (Millimoles Per Liter (mmol/L))	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.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^9 Cells Per Liter (10^9 Cells/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Haematology (Percentage (%) of Cells)	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.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Haematology (Liter Per Liter (L/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Haematology (Grams Per Liter (g/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Clinical Laboratory Parameters: Haematology (10^12 Cells Per Liter (10^12/L))	BL denotes Baseline, CFB denotes Change from Baseline and W denotes Week for the reported categories.	Baseline, Week 338
Change From Baseline in Vital Signs: Blood Pressure	BL denotes BL, CFB denotes Change from baseline and W denotes Week for the reported categories.	Baseline, Week 338
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	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.	Baseline to Week 338
Number of Participants With Potentially Clinically Significant Vital Signs	Data is reported only for participants who had potentially clinically significant values.	Baseline to Week 338
Number of Participants With Potentially Clinically Significant Weight and Height	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.	Baseline to Week 338
Number of Participants With Potentially Clinically Significant ECG Evaluations		Baseline to Week 338

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in All Seizure 28-day Frequency	Change from Baseline is denoted as CFB.	Baseline, Week 252
Percent Change From Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut Syndrome [LGS] Participants)	Change from Baseline is denoted as CFB.	Baseline, Week 252
Percent Change From Baseline in Convulsive Seizure 28-day Frequency (Dravet Syndrome [DS] Participants)	Change from Baseline is denoted as CFB.	Baseline, Week 252
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)	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.	Baseline, Week 336

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2018
• Primary Completion (Actual): July 30, 2025
• Study Completion (Actual): July 30, 2025

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 15, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy; Soticlestat
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Epilepsy, Generalized; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Epilepsy; Epilepsies, Myoclonic; Lennox Gastaut Syndrome; soticlestat
• Other Study ID Numbers: TAK-935-18-001; U1111-1218-5515 (Other Identifier: WHO); 2018-002485-39 (EudraCT Number); 2022-502801-13-00 (Ctis: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No