Clinical trial NCT04940624: A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet 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 Young Adult Subjects With Dravet Syndrome (DS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dravet Syndrome (DS)
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-06-25
Enrollment: 144
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 convulsive seizures in children and young adults with DS.

Participants will receive their standard antiseizure therapy, plus either a tablet of soticlestat or placebo for 16 weeks. A placebo looks just like soticlestat but will not have any medicine in it.

Participants may continue treatment in an extension study, based on the extension study's entry criteria. Those that want to stop treatment will have a gradual dose reduction during 1 week and then be followed up for 2 weeks.

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

The study will enroll approximately 142 pediatric and young adult patients. Participants will be randomized at a 1:1 ratio to receive standard of care (SOC) plus one of the following adjunctive therapies:

* Soticlestat or
* Placebo

The total daily dose of study drug will be calculated based on body weight in the 4 weeks Titration Period. Following the Titration Period, participants will continue to receive the same dose in the 12-weeks Maintenance Period.

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 Full 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 DS.
2. Had ≥12 convulsive seizures over 12 weeks before screening based on the historical information and has had ≥4 convulsive 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 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 4 ASMs at stable doses for at least 4 weeks before the screening visit (Visit 1); benzodiazepines used chronically (daily) to treat seizures are considered ASMs. Fenfluramine and cannabidiol (Epidiolex) are allowed where available and should be counted as an ASM. ASM dosing regimen must remain constant throughout the 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.

Primary outcomes:
measure: Percent Change From Baseline in Convulsive 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 Convulsive Seizure Frequency Per 28 Days During the Maintenance Period
timeFrame: Baseline; Maintenance Period: Weeks 5 to 16
Secondary outcomes:
measure: Percentage of Responders During 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%, and >75% to ≤100% Reduction in Convulsive Seizures 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 Convulsive Seizure-free Days During the Full Treatment Period
timeFrame: Baseline up to Week 16
measure: Longest Convulsive 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: 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: 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: 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: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Multicare Health System - Mary Bridge Pediatrics
state: Washington
city: South Brisbane
country: Australia
facility: Queensland Childrens Hospital
state: Queensland
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: Sao Paulo
country: Brazil
facility: Universidade de Sao Paulo
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: 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: 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
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: Chaidari
country: Greece
facility: Attikon University General Hospital
state: Attiki
city: Budapest
country: Hungary
facility: Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet
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: 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: 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: 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: 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: Neurosphera SP. Z O.O
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: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical University n.a. V.F. Voyno-Ysenetskiy
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: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga Hospital General
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
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
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: