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: Active, not recruiting
• 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
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital of Fudan University
• Israel
  • Be'er Sheva, Israel, 84101
    • Soroka University Medical Centre
  • Beer Sheva, Israel, 84101
    • Soroka University Medical Centre
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Holon, Israel, 58100
    • Edith Wolfson Medical Center
  • Petach Tikva, Israel, 49100
    • Schneider Children's Medical Center of Israel - Petah Tikvah - PIN
  • 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
  • Warszawa, Poland, 02-091
    • Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne
  • Swietokrzyskie
    • Kielce, Swietokrzyskie, Poland, 25-316
      • NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-355
      • Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
• Portugal
  • Lisboa, Portugal, 1169-045
    • Centro Hospitalar Lisboa Central- Hospital Dona Estefania
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
  • Lisboa, Portugal, 1600-035
    • 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)
  • Navarra
    • Pamplona, Navarra, 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: 7 months 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; 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; 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 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

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 (Estimated): May 22, 2026
• Study Completion (Estimated): May 22, 2026

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 (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

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