A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
- Conditions
- Dravet Syndrome (DS)Lennox Gastaut Syndrome (LGS)
- Interventions
- Registration Number
- NCT05163314
- Lead Sponsor
- Takeda
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 400
- Participant must have:
- Been previously enrolled in a phase 3 soticlestat clinical study.
- 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.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Soticlestat Soticlestat Participants with DS and LGS will receive:Participants weighing \<45kg:Soticlestat,mini-tablets,titrated from lower dose level(60mg to 140mg) to higher dose(100mg to 200mg) twice daily(BID),based on body weight,orally/via enteral feeding tubes including but not limited to nasogastric(NG)-tube,gastrostomy tube(G-tube),MIC-KEY button,upto 2 weeks in Titration Period. Will continue to receive dose they are on at end of Titration Period,for approximately 4 years in Maintenance Period.Dose will be tapered down to lower dose(not less than lowest dose level based on weight)every 3 days until study drug is discontinued(upto 1week) in Taper Period.Participants weighing ≥45kg/adults:Soticlestat mini-tablets/tablets with starting dose of 200mg BID followed by 300mg BID,up to 2 weeks in Titration Period.Will continue to receive 300mg BID for approximately 4 years in Maintenance Period.Dose will be tapered down upto 100mg every 3 days until study drug is discontinued(up to 1 week) in Taper Period.
- Primary Outcome Measures
Name Time Method Change from Baseline in Body Weight for All Age Groups Up to 4 years Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score Up to 4 years C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation.
Change from Baseline in Height for All Age Groups Up to 4 years Absolute Value for Insulin-like Growth Factor 1 (IGF-1) for Children 2 to 17 Years of Age During the Study Up to 4 years Absolute Value for Tanner Stage for Children 6 to 17 Years of Age During the Study Up to 4 years Tanner assessment score is 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).
Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) Up to 4 years An Adverse Event (AE) is 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 can therefore be 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 is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
- Secondary Outcome Measures
Name Time Method Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency per 28 Days in LGS Cohort Up to 4 years MMD seizure frequency per 28 days is defined as total number of MMD seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline will be 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.
Clinical Global Impression of Improvement (CGI-I) Score Up to 4 years The CGI-I Clinician is a 7-point Likert scale that the investigator uses to rate a participant's change (improvement) in overall seizure control, behavior, safety and tolerability, after the initiation of study drug relative to Baseline (before treatment with study drug). The participant will be 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). Higher score will indicate worse symptoms.
Change in Quality of Life Inventory-Disability (QI-Disability) Score Up to 4 years 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. Scores are from a 5-point Likert scale and then are transformed to a scale of 0 to 100. Possible scores range from 0-100, with higher scores indicating better quality of life.
Percent Change from Baseline in Convulsive Seizure Frequency per 28 Days in DS Cohort Up to 4 years Convulsive seizure frequency per 28 days is 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 will be 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 Total Seizure Frequency per 28 Days for DS and LGS Participants Up to 4 years Seizure frequency per 28 days is 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 is 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.
CGI-I Seizure Intensity and Duration Score Up to 4 years The CGI-I seizure intensity and duration instrument is used by the parent/caregiver to rate improvement in intensity and duration of convulsive seizures (DS Cohort) or MMD seizures (LGS Cohort) from Baseline. The participant's symptoms will be 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). Higher score will indicate worse symptoms.
Caregiver Global Impression of Improvement (Care GI-I) Score Up to 4 years The Care GI-I is a 7-point Likert scale that the caregiver uses to rate improvement in overall seizure control, behavior, safety and tolerability after the initiation of study drug relative to Baseline (before treatment with study drug). The participant will be 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 will complete the Care GI-I via interview. Higher score will indicate worse symptoms.
CGI-I Nonseizure Symptoms Score Up to 4 years The CGI-I nonseizure symptoms instrument is a series of single-item assessments that the investigator uses to rate improvement in the symptoms and impacts in select nonseizure domains since initiating the study drug. The participant will be 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 is completed by the clinician in collaboration with the primary caregiver to assess the participants status based on the presence of any nonseizure symptoms. Higher score will indicate worse symptoms.
Trial Locations
- Locations (115)
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Center For Neurosciences
🇺🇸Tucson, Arizona, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
University of California Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Colorado Children's Hospital
🇺🇸Denver, Colorado, United States
Pediatric Neurology PA
🇺🇸Winter Park, Florida, United States
Clinical Integrative Research Center of Atlanta
🇺🇸Atlanta, Georgia, United States
Sunrise Pediatric Neurology
🇺🇸Marietta, Georgia, United States
University of Iowa Hospitals & Clinics - (CRS)
🇺🇸Iowa City, Iowa, United States
Midatlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
Minnesota Epilepsy Group PA
🇺🇸Saint Paul, Minnesota, United States
Institute of Neurology and Neurosurgery at Saint Barnabas, LLC
🇺🇸Livingston, New Jersey, United States
Boston Children's Health Physicians (BCHP)
🇺🇸New York, New York, United States
Northwell Health Physician Partners - Neurology at Lenox Hill
🇺🇸New York, New York, United States
NYU Comprehensive Epilepsy Center
🇺🇸New York, New York, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
WellSpan Oncology Research
🇺🇸York, Pennsylvania, United States
Medical University of South Carolina Children Hospital - PIN
🇺🇸Charleston, South Carolina, United States
Cook Children's Medical Center - Jane and John Justin Neurosciences Center
🇺🇸Fort Worth, Texas, United States
University of Utah - Primary Children's Hospital - PPDS
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
MultiCare Institute for Research & Innovation (Tacoma)
🇺🇸Tacoma, Washington, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
Queensland Childrens Hospital
🇦🇺Brisbane, Queensland, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
UZ Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
Centre Neurologique William Lennox
🇧🇪Ottignies-Louvain-la-Neuve, Brabant Wallon, Belgium
Hopital Universitaire des Enfants Reine Fabiola
🇧🇪Brussel, Brussels, Belgium
Instituto de Neurologia de Curitiba (INC)
🇧🇷Curitiba, Parana, Brazil
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital das Clinicas - UNICAMP
🇧🇷Campinas, Sao Paulo, Brazil
Universidade Federal de Sao Paulo
🇧🇷Sao Paulo, Brazil
Universidade de Sao Paulo
🇧🇷Sao Paulo, Brazil
Child and Family Research Institute
🇨🇦Vancouver, British Columbia, Canada
Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Beijing Children's Hospital,Capital Medical University
🇨🇳Beijing, Beijing, China
Children's Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
The Second Affiliated Hospital of Guangzhou Medical Univeristy
🇨🇳Guangzhou, Guangdong, China
Guangzhou Women And Children's Medical Center
🇨🇳Guangzhou, Guangdong, China
Shenzhen Children's Hospital
🇨🇳Shenzhen, Guangdong, China
Wuhan Childrens hospital
🇨🇳Wuhan, Hubei, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Jiangxi Provincial Children's Hospital
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Children's Hospital of Shanghai
🇨🇳Shanghai, Shanghai, China
Children's Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Hopitaux de La Timone
🇫🇷Marseille, Bouches-du-Rhone, France
CHRU Dijon Hopital General
🇫🇷Dijon, Cote-d'Or, France
Hopital Roger Salengro
🇫🇷Lille, Nord, France
Hopital Necker - Enfants Malades
🇫🇷Paris, France
Hopital Robert Debre
🇫🇷Paris, France
Alberta Childrens Hospital
🇩🇪Freiburg, Baden-Wurttemberg, Germany
Klinikum der Johann-Wolfgang Goethe-Universitat
🇩🇪Frankfurt am Main, Hessen, Germany
Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel
🇩🇪Bielefeld, Nordrhein-Westfalen, Germany
Kleinwachau Sachsisches Epilepsiezentrum Radeberg Gemeinnutzige Gmbh
🇩🇪Radeberg, Sachsen, Germany
Childrens' Hospital of Athens 'P. and A. Kyriakou'
🇬🇷Athens, Attiki, Greece
Attikon University General Hospital
🇬🇷Chaidari, Attiki, Greece
University General Hospital of Larissa
🇬🇷Larisa, Greece
Hippokration Hospital
🇬🇷Thessaloniki, Greece
Pecsi Tudomanyegyetem
🇭🇺Pecs, Baranya, Hungary
Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak
🇭🇺Budapest, Hungary
Bethesda Gyermekkorhaz
🇭🇺Budapest, Hungary
Orszagos Klinikai Idegtudomanyi Intezet
🇭🇺Budapest, Hungary
Ospedale Bellaria
🇮🇹Roma, Lazio, Italy
IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN
🇮🇹Roma, Lazio, Italy
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
ASST di Mantova - Azienda Ospedaliera Carlo Poma
🇮🇹Mantova, Lombardia, Italy
ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS
🇮🇹Pavia, Lombardia, Italy
Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN
🇮🇹Firenze, Toscana, Italy
Aichi Medical University Hospital
🇯🇵Nagakute-Shi, Aiti, Japan
Fukuoka Children's Hospital
🇯🇵Fukuoka-Shi, Hukuoka, Japan
Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
🇯🇵Yokohama-Shi, Kanagawa, Japan
Kumamoto-Ezuko Medical Center for The Severely Disabled
🇯🇵Kumamoto-Shi, Kumamoto, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵Omura-Shi, Nagasaki, Japan
National Hospital Organization Nishi-Niigata Chuo National Hospital
🇯🇵Niigata-Shi, Niigata, Japan
Okayama University Hospital
🇯🇵Okayama-city, Okayama, Japan
Yasuhara Childrens Clinic
🇯🇵Neyagawa-Shi, Osaka, Japan
Osaka City General Hospital
🇯🇵Osaka-Shi, Osaka, Japan
Osaka University Hospital
🇯🇵Suita-Shi, Osaka, Japan
National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders
🇯🇵Shizuoka-Shi, Sizuoka, Japan
Hokkaido University Hospital
🇯🇵Chuo-Ku, Tokyo, Japan
National Center of Neurology and Psychiatry
🇯🇵Kodaira-Shi, Tokyo, Japan
Childrens University Hospital
🇱🇻Riga, Latvia
Hospital Civil Fray Antonio Alcalde
🇲🇽El Retiro, Jalisco, Mexico
Kempenhaeghe - PPDS
🇳🇱Heeze, Noord-Brabant, Netherlands
Stichting Epilepsie Instellingen Nederland
🇳🇱Zwolle, Overijssel, Netherlands
Centrum Medyczne Plejady
🇵🇱Krakow, Malopolskie, Poland
Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego w Warszawie
🇵🇱Warszawa, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Russian National Research Medical University n.a. N.I.Pirogov
🇷🇺Moscow, Russian Federation
UGMK-Zdorojie, LLC
🇷🇺Ekaterinburg, Russian Federation
Krasnoyarsk State Medical University n.a. V.F. Voyno-Ysenetskiy
🇷🇺Krasnoyarsk, Russian Federation
Tyumen State Medical Academy
🇷🇺Tyumen', Russian Federation
Clinic for Neurology and Psychiatry for Children and Youth
🇷🇸Belgrade, Serbia
Mother and Child Health Care Institute of Serbia Dr Vukan Cupic
🇷🇸Belgrade, Serbia
University Clinical Center Nis
🇷🇸Nis, Serbia
Children and Youth Health Care Institute of Vojvodina
🇷🇸Novi Sad, Serbia
Clinica Universidad Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Regional Universitario de Malaga Hospital General
🇪🇸Almeria, Spain
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸Barcelona, Spain
Hospital Vithas La Salud
🇪🇸Granada, Spain
Centro de Neurologia Avanzada
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Municipal Institution Dnipropetrovsk Regional Children Clinical Hospital of DRC
🇺🇦Dnipro, Dnipropetrovs'ka Oblast, Ukraine
Communal Non-profit Enterprise Dnipro City Children Clinical Hospital #5 of DCC
🇺🇦Dnipro, Dnipropetrovs'ka Oblast, Ukraine
Communal Non-commercial Enterprise Iv-Frank Regional Childrens Clinical Hosp of Iv-Frank RC
🇺🇦Ivano-Frankivsk, Ukraine
CNPE Clinical Hospital Psychiatry of the Executive Body of the Kyiv City Council KCSA
🇺🇦Kyiv, Ukraine
SI Ukr. Med. Rehabilitation Center For Children With Organic Injury of Nervous System of MoH of Ukr
🇺🇦Kyiv, Ukraine