Clinical trial NCT04938427: A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Soticlestat as Adjunctive Therapy in Pediatric and Adult Subjects With Lennox-Gastaut Syndrome (LGS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lennox Gastaut Syndrome (LGS)
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-06-24
Enrollment: 270
Sex: ALL
Minimum age (years): 2
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aims of the study are:

* to learn if soticlestat, when given as add-on therapy, reduces the number of major motor drop seizures in children, teenagers, and adults with Lennox-Gastaut Syndrome.
* to assess the safety profile of soticlestat when given in combination with other therapies.

Participants will receive their standard antiseizure therapy, plus either tablets of soticlestat or placebo. A placebo looks just like soticlestat but will not have any medicine in it. Participants will take soticlestat or placebo for 16 weeks, followed by a gradual dose reduction for 1 week. Then, participants will be followed up for 2 weeks.

Detailed description: The drug being tested in this study is called soticlestat (TAK-935). Soticlestat will be assessed for efficacy, safety, and tolerability in pediatric and adult participants with LGS.

The study will enroll approximately 234 patients. Participants will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to receive standard of care (SOC) plus one of the following adjunctive therapies which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

1. Soticlestat
2. Placebo (dummy inactive pill - this is a tablet/mini-tablet that looks like the study drug but has no active ingredient)

Participants will receive soticlestat or matching placebo based on their weight in the 4-week Titration Period. Following the Titration Period, participants will continue to receive the same dose in the 12-week Maintenance Period. The dose will then be down-tapered if participants decide to discontinue the treatment and/or are not deemed eligible to continue in Open-label extension (OLE).

This multi-center trial will be conducted worldwide. The overall time to participate in the study will be from 22-25 weeks. At the end of the treatment period, participants have the option to either complete the study and taper off the investigational product or to enter the OLE if they meet eligibility requirements. If participants discontinue, they will be followed-up on phone call approximately 14 days after the last dose of study drug for safety.

Eligibility criteria: Inclusion Criteria:

1. Has documented clinical diagnosis of LGS.
2. Has had ≥8 MMD seizures each month in the 3 months prior to Screening based on the historical information and has had ≥8 MMD seizures per 28 days during the 4 to 6 week prospective Baseline Period.
3. Weighs ≥10 kg at the Screening Visit (Visit 1).
4. Failure to control seizures despite appropriate trials of at least 1 ASM based on historical information, and is currently on an antiseizure therapy or other treatment options considered as standard of care (SOC).
5. Artisanal cannabidiols are allowed at a stable dose for at least 4 weeks before the screening visit (Visit 1); the dosing regimen and manufacturer should remain constant throughout the study. (Artisanal cannabidiols will not be counted as ASMs.)
6. Currently taking 0 to 3 ASMs at stable doses for at least 4 weeks before the Screening Visit (Visit 1); Fenfluramine and cannabidiol (Epidiolex) are allowed where available and counted as an ASM. ASM dosing regimen must remain constant throughout the study.

Exclusion Criteria:

1. Admitted to a medical facility and intubated for treatment of status epilepticus 2 or more times in the 3 months immediately before Screening (Visit 1). For the purpose of this exclusion criterion, status is defined as continuous seizure activity lasting longer than 5 minutes or repeated seizures without return to Baseline in between seizures.
2. 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.
3. Considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the participant has attempted suicide within 12 months before the Screening Visit (Visit 1). Participants who have positive answers on item numbers 4 or 5 on the Columbia suicide severity rating scale (C-SSRS) before dosing (Visit 2) are excluded. This scale will only be administered to participants aged ≥6 years.

Primary outcomes:
measure: Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Full Treatment Period
timeFrame: Baseline; Full Treatment Period: Weeks 1 to 16
measure: Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Maintenance Period
timeFrame: Baseline; Maintenance Period: Weeks 5 to 16
Secondary outcomes:
measure: Percentage of Responders During the Maintenance Period
timeFrame: Maintenance Period: Weeks 5 to 16
measure: Percentage of Responders During the Full Treatment Period
timeFrame: Full Treatment Period: Weeks 1 to 16
measure: Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, >75% to ≤100% Reduction in MMD Seizure During the Full Treatment Period
timeFrame: Full Treatment Period: Weeks 1 to 16
measure: Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16
timeFrame: Week 16
measure: Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16
timeFrame: Week 16
measure: Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16
timeFrame: Week 16
measure: Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period
timeFrame: Baseline; Maintenance Period: Weeks 5 to 16
measure: Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period
timeFrame: Baseline; Full Treatment Period: Weeks 1 to 16
measure: Change From Baseline in Percentage of MMD Seizure-free Days During the Full Treatment Period
timeFrame: Baseline up to Week 16
measure: Longest MMD Seizure-free Interval During the Full Treatment Period
timeFrame: Full Treatment Period: Weeks 1 to 16
measure: Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period
timeFrame: Full Treatment Period: Weeks 1 to 16
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: Children's Hospital Colorado.
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: 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: Roseville
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: Premier Healthcare Inc.
state: New York
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center
state: New York
city: New York
country: United States
facility: Northwell Health Physician Partners - Neurology at Lenox Hill
state: New York
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: South 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 PIN
state: Antwerpen
city: Ottignies-Louvain-la-Neuve
country: Belgium
facility: Centre Neurologique William Lennox
state: Brabant Wallon
city: Brussels
country: Belgium
facility: Hopital Universitaire des Enfants Reine Fabiola
city: Calgary
country: Canada
facility: Alberta Childrens Hospital
state: Alberta
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 University
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 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: Dijon
country: France
facility: CHRU Dijon Hopital General
state: Cote-d'Or
city: Lille
country: France
facility: Hopital Roger Salengro
state: Nord
city: Marseille
country: France
facility: Hopitaux de La Timone
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Paris
country: France
facility: Hopital Robert Debre
city: Vogtareuth
country: Germany
facility: Schon Klinik Vogtareuth
state: Bayern
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: Sachse
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 Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet
city: Bologna
country: Italy
facility: Ospedale Bellaria
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
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: 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: Kodaira-Shi
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Riga
country: Latvia
facility: Childrens University Hospital
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: 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: Ekaterinburg
country: Russian Federation
facility: UGMK-Zdorojie, LLC
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: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga Hospital General
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 City Childrens Clinical Hospital #6 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: Medical Director
role: STUDY_DIRECTOR
References: