Clinical trial NCT05163314: A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
Official title: A Phase 3, Prospective, Open-Label, Multisite, Extension of Phase 3 Studies To Assess the Long-Term Safety and Tolerability of Soticlestat as Adjunctive Therapy in Subjects With Dravet Syndrome or Lennox-Gastaut Syndrome (ENDYMION 2)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Dravet Syndrome (DS)
Lennox Gastaut Syndrome (LGS)
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-12-20
Enrollment: 400
Sex: ALL
Minimum age (years): 2
Maximum age (years): 56
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to 4 years
measure: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Up to 4 years
measure: Change from Baseline in Body Weight for All Age Groups
timeFrame: Up to 4 years
measure: Change from Baseline in Height for All Age Groups
timeFrame: Up to 4 years
measure: Absolute Value for Tanner Stage for Children 6 to 17 Years of Age During the Study
timeFrame: Up to 4 years
measure: Absolute Value for Insulin-like Growth Factor 1 (IGF-1) for Children 2 to 17 Years of Age During the Study
timeFrame: Up to 4 years
Secondary outcomes:
measure: Percent Change from Baseline in Total Seizure Frequency per 28 Days for DS and LGS Participants
timeFrame: Up to 4 years
measure: Percent Change from Baseline in Convulsive Seizure Frequency per 28 Days in DS Cohort
timeFrame: Up to 4 years
measure: Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency per 28 Days in LGS Cohort
timeFrame: Up to 4 years
measure: Clinical Global Impression of Improvement (CGI-I) Score
timeFrame: Up to 4 years
measure: Caregiver Global Impression of Improvement (Care GI-I) Score
timeFrame: Up to 4 years
measure: CGI-I Seizure Intensity and Duration Score
timeFrame: Up to 4 years
measure: CGI-I Nonseizure Symptoms Score
timeFrame: Up to 4 years
measure: Change in Quality of Life Inventory-Disability (QI-Disability) Score
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Tucson
country: United States
facility: Center For Neurosciences
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: San Francisco
country: United States
facility: University of California Benioff Children's Hospital
state: California
city: Denver
country: United States
facility: Colorado Children's Hospital
state: Colorado
city: Winter Park
country: United States
facility: Pediatric Neurology PA
state: Florida
city: Atlanta
country: United States
facility: Clinical Integrative Research Center of Atlanta
state: Georgia
city: Marietta
country: United States
facility: Sunrise Pediatric Neurology
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics - (CRS)
state: Iowa
city: Bethesda
country: United States
facility: Midatlantic Epilepsy and Sleep Center
state: Maryland
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group PA
state: Minnesota
city: Livingston
country: United States
facility: Institute of Neurology and Neurosurgery at Saint Barnabas, LLC
state: New Jersey
city: New York
country: United States
facility: Boston Children's Health Physicians (BCHP)
state: New York
city: New York
country: United States
facility: Northwell Health Physician Partners - Neurology at Lenox Hill
state: New York
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center
state: New York
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: York
country: United States
facility: WellSpan Oncology Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina Children 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: Salt Lake City
country: United States
facility: University of Utah - Primary Children's Hospital - PPDS
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation (Tacoma)
state: Washington
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Childrens Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Ottignies-Louvain-la-Neuve
country: Belgium
facility: Centre Neurologique William Lennox
state: Brabant Wallon
city: Brussel
country: Belgium
facility: Hopital Universitaire des Enfants Reine Fabiola
state: Brussels
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba (INC)
state: Parana
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Hospital das Clinicas - UNICAMP
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo
city: Sao Paulo
country: Brazil
facility: Universidade de Sao Paulo
city: Vancouver
country: Canada
facility: Child and Family Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Children's Hospital,Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical Univeristy
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Women And Children's Medical Center
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
state: Guangdong
city: Wuhan
country: China
facility: Wuhan Childrens hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Provincial Children's Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Children's Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
city: Marseille
country: France
facility: Hopitaux de La Timone
state: Bouches-du-Rhone
city: Dijon
country: France
facility: CHRU Dijon Hopital General
state: Cote-d'Or
city: Lille
country: France
facility: Hopital Roger Salengro
state: Nord
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Paris
country: France
facility: Hopital Robert Debre
city: Freiburg
country: Germany
facility: Alberta Childrens Hospital
state: Baden-Wurttemberg
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe-Universitat
state: Hessen
city: Bielefeld
country: Germany
facility: Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel
state: Nordrhein-Westfalen
city: Radeberg
country: Germany
facility: Kleinwachau Sachsisches Epilepsiezentrum Radeberg Gemeinnutzige Gmbh
state: Sachsen
city: Athens
country: Greece
facility: Childrens' Hospital of Athens 'P. and A. Kyriakou'
state: Attiki
city: Chaidari
country: Greece
facility: Attikon University General Hospital
state: Attiki
city: Larisa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: Hippokration Hospital
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem
state: Baranya
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak
city: Budapest
country: Hungary
facility: Bethesda Gyermekkorhaz
city: Budapest
country: Hungary
facility: Orszagos Klinikai Idegtudomanyi Intezet
city: Roma
country: Italy
facility: Ospedale Bellaria
state: Lazio
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Mantova
country: Italy
facility: ASST di Mantova - Azienda Ospedaliera Carlo Poma
state: Lombardia
city: Pavia
country: Italy
facility: ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN
state: Toscana
city: Nagakute-Shi
country: Japan
facility: Aichi Medical University Hospital
state: Aiti
city: Fukuoka-Shi
country: Japan
facility: Fukuoka Children's Hospital
state: Hukuoka
city: Yokohama-Shi
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
state: Kanagawa
city: Kumamoto-Shi
country: Japan
facility: Kumamoto-Ezuko Medical Center for The Severely Disabled
state: Kumamoto
city: Omura-Shi
country: Japan
facility: National Hospital Organization Nagasaki Medical Center
state: Nagasaki
city: Niigata-Shi
country: Japan
facility: National Hospital Organization Nishi-Niigata Chuo National Hospital
state: Niigata
city: Okayama-city
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Neyagawa-Shi
country: Japan
facility: Yasuhara Childrens Clinic
state: Osaka
city: Osaka-Shi
country: Japan
facility: Osaka City General Hospital
state: Osaka
city: Suita-Shi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Shizuoka-Shi
country: Japan
facility: National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders
state: Sizuoka
city: Chuo-Ku
country: Japan
facility: Hokkaido University Hospital
state: Tokyo
city: Kodaira-Shi
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Riga
country: Latvia
facility: Childrens University Hospital
city: El Retiro
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
state: Jalisco
city: Heeze
country: Netherlands
facility: Kempenhaeghe - PPDS
state: Noord-Brabant
city: Zwolle
country: Netherlands
facility: Stichting Epilepsie Instellingen Nederland
state: Overijssel
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
state: Malopolskie
city: Warszawa
country: Poland
facility: Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego w Warszawie
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Poznan
country: Poland
facility: Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University n.a. N.I.Pirogov
state: Moskva
city: Ekaterinburg
country: Russian Federation
facility: UGMK-Zdorojie, LLC
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical University n.a. V.F. Voyno-Ysenetskiy
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University n.a. N.I.Pirogov
city: Tyumen'
country: Russian Federation
facility: Tyumen State Medical Academy
city: Belgrade
country: Serbia
facility: Clinic for Neurology and Psychiatry for Children and Youth
city: Belgrade
country: Serbia
facility: Mother and Child Health Care Institute of Serbia Dr Vukan Cupic
city: Nis
country: Serbia
facility: University Clinical Center Nis
city: Novi Sad
country: Serbia
facility: Children and Youth Health Care Institute of Vojvodina
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
state: Navarra
city: Almeria
country: Spain
facility: Hospital Regional Universitario de Malaga Hospital General
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Granada
country: Spain
facility: Hospital Vithas La Salud
city: Sevilla
country: Spain
facility: Centro de Neurologia Avanzada
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Dnipro
country: Ukraine
facility: Municipal Institution Dnipropetrovsk Regional Children Clinical Hospital of DRC
state: Dnipropetrovs'ka Oblast
city: Dnipro
country: Ukraine
facility: Communal Non-profit Enterprise Dnipro City Children Clinical Hospital #5 of DCC
state: Dnipropetrovs'ka Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Communal Non-commercial Enterprise Iv-Frank Regional Childrens Clinical Hosp of Iv-Frank RC
city: Kyiv
country: Ukraine
facility: CNPE Clinical Hospital Psychiatry of the Executive Body of the Kyiv City Council KCSA
city: Kyiv
country: Ukraine
facility: SI Ukr. Med. Rehabilitation Center For Children With Organic Injury of Nervous System of MoH of Ukr
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: