Clinical trial NCT03635073: A Study of Soticlestat in Adults and Children With Rare Epilepsies
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Epilepsy
Dravet Syndrome (DS)
Lennox-Gastaut Syndrome (LGS)
Keywords: Soticlestat
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-08-17
Enrollment: 156
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experience At least one Adverse Event (AE)
timeFrame: Up to 6 years
measure: Change from Baseline in Behavioral and Adaptive Functional Measures Using the Vineland Adaptive Behavior Scale (VABS)
timeFrame: Up to 6 years
measure: 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
timeFrame: Up to 6 years
measure: 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
timeFrame: Up to 6 years
Secondary outcomes:
measure: Percent Change from Baseline in all Seizure 28-day Frequency
timeFrame: Up to 6 years
measure: Percent Change from Baseline in Drop Seizure 28-day Frequency (Lennox-Gastaut syndrome [LGS] Participants)
timeFrame: Up to 6 years
measure: Percent Change from Baseline in Convulsive Seizure 28-day Frequency (Dravet syndrome [DS] Participants)
timeFrame: Up to 6 years
measure: Percent Change from Baseline in Motor Seizure 28-day Frequency
timeFrame: Up to 6 years
measure: Change from Baseline in Clinician's Clinical Global Impression of Severity (CGI-S)
timeFrame: Up to 6 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenosciences Inc
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Aurora
country: United States
facility: Colorado Children's Hospital
state: Colorado
city: Aurora
country: United States
facility: Colorado Children's Hospital
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center Inc
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center Inc
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Winter Park
country: United States
facility: Pediatric Neurology PA
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Norcross
country: United States
facility: Center for Rare Neurological Diseases
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research LLC
state: Kentucky
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - PIN
state: Minnesota
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group PA
state: Minnesota
city: Chesterfield
country: United States
facility: Max Benzaquen, M.D., PC
state: Missouri
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: New Brunswick
country: United States
facility: Children's Hospital at Saint Peter's University Hospital
state: New Jersey
city: New York
country: United States
facility: NYU - Ambulatory Care Center (ACC)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - PIN
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center - PPDS
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina Childrens Hospital - PIN
state: South Carolina
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Jane and John Justin Neurosciences Center
state: Texas
city: Clayton
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Heidelberg West
country: Australia
facility: Austin Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
state: Guangdong
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Children's Hospital,Capital Medical University
city: Beijing
country: China
facility: Beijing Children's Hospital,Capital Medical University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
state: Tel-Aviv
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Centre
city: Beer Sheva
country: Israel
facility: Soroka University Medical Centre
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel - Petah Tikvah - PIN
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel - Petah Tikvah - PIN
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center - PPDS
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center - PPDS
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Kielce
country: Poland
facility: NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
state: Swietokrzyskie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
state: Wielkopolskie
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Warsaw
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Central- Hospital Dona Estefania
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
city: Madrid
country: Spain
facility: Hospital Ruber Internacional (Grupo Quironsalud)
state: Madrid, Communidad Delaware
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
state: Navarra
city: Granada
country: Spain
facility: Hospital Vithas La Salud
city: Madrid
country: Spain
facility: Hospital Ruber Internacional (Grupo Quironsalud)
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
References: