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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04938427




Registration number
NCT04938427
Ethics application status
Date submitted
18/06/2021
Date registered
24/06/2021

Titles & IDs
Public title
A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome
Scientific 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)
Secondary ID [1] 0 0
2021-002481-40
Secondary ID [2] 0 0
TAK-935-3002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lennox Gastaut Syndrome (LGS) 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Soticlestat

Placebo comparator: Placebo - Soticlestat placebo-matching mini-tablets or tablets, orally or via G-tube or MIC-KEY button or J-tube, BID, up to 4 weeks during titration. Participants continued to receive soticlestat placebo-matching mini-tablets or tablets for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period). Soticlestat matching tapering was done to maintain the blind if participants decided to discontinue the treatment.

Experimental: Soticlestat - Participants weighing \<45 kg: Soticlestat, mini-tablets, at the dose of 40 mg to 200 mg, orally or via G-tube or MIC-KEY button or J-tube, BID based on body weight up to 4 weeks during titration. Participants continued to receive the dose that they were on at the end of the titration, for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period) with the dose tapered down if participants decided to discontinue the treatment.

Participants weighing =45 kg: Soticlestat mini-tablets or tablets with a starting dose of 100 mg BID followed by 200 mg BID and, then 300 mg BID, up to 4 weeks during titration. Participants continued to receive 300 mg BID for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period) with the dose tapered down if participants decided to discontinue the treatment.


Treatment: Drugs: Placebo
Soticlestat placebo-matching mini-tablets or tablets.

Treatment: Drugs: Soticlestat
Soticlestat mini-tablets or tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Full Treatment Period
Timepoint [1] 0 0
Baseline; Full Treatment Period: Weeks 1 to 16
Primary outcome [2] 0 0
Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Maintenance Period
Timepoint [2] 0 0
Baseline; Maintenance Period: Weeks 5 to 16
Secondary outcome [1] 0 0
Percentage of Responders During the Maintenance Period
Timepoint [1] 0 0
Maintenance Period: Weeks 5 to 16
Secondary outcome [2] 0 0
Percentage of Responders During the Full Treatment Period
Timepoint [2] 0 0
Full Treatment Period: Weeks 1 to 16
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Full Treatment Period: Weeks 1 to 16
Secondary outcome [4] 0 0
Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16
Timepoint [4] 0 0
Week 16
Secondary outcome [5] 0 0
Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16
Timepoint [5] 0 0
Week 16
Secondary outcome [6] 0 0
Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16
Timepoint [6] 0 0
Week 16
Secondary outcome [7] 0 0
Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16
Timepoint [7] 0 0
Baseline, Week 16
Secondary outcome [8] 0 0
Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16
Timepoint [8] 0 0
Week 16
Secondary outcome [9] 0 0
Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period
Timepoint [9] 0 0
Baseline; Maintenance Period: Weeks 5 to 16
Secondary outcome [10] 0 0
Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period
Timepoint [10] 0 0
Baseline; Full Treatment Period: Weeks 1 to 16
Secondary outcome [11] 0 0
Change From Baseline in Percentage of MMD Seizure-free Days During the Full Treatment Period
Timepoint [11] 0 0
Baseline up to Week 16
Secondary outcome [12] 0 0
Longest MMD Seizure-free Interval During the Full Treatment Period
Timepoint [12] 0 0
Full Treatment Period: Weeks 1 to 16
Secondary outcome [13] 0 0
Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period
Timepoint [13] 0 0
Full Treatment Period: Weeks 1 to 16

Eligibility
Key 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.
Minimum age
2 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/01/2024
Sample size
Target
Accrual to date
Final
270
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Queensland Childrens Hospital - South Brisbane
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Belgium
State/province [17] 0 0
Antwerpen
Country [18] 0 0
Belgium
State/province [18] 0 0
Brabant Wallon
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussels
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
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China
State/province [23] 0 0
Beijing
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China
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Chongqing
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China
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Guangdong
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China
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Hubei
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China
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Hunan
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China
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Jiangxi
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China
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Jilin
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China
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Shanghai
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France
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Cote-d'Or
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France
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Nord
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France
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Marseille
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France
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Paris
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Germany
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Bayern
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Germany
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Hessen
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Germany
State/province [37] 0 0
Nordrhein-Westfalen
Country [38] 0 0
Germany
State/province [38] 0 0
Sachse
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Greece
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Attiki
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Greece
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Larisa
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Greece
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Thessaloniki
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Hungary
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Baranya
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Hungary
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Budapest
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Italy
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Emilia-Romagna
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Toscana
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Japan
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Aiti
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Japan
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Hukuoka
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Japan
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Kumamoto
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Japan
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Nagasaki
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Japan
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Niigata
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Sizuoka
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Japan
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Tokyo
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Latvia
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Riga
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Netherlands
State/province [58] 0 0
Noord-Brabant
Country [59] 0 0
Netherlands
State/province [59] 0 0
Overijssel
Country [60] 0 0
Poland
State/province [60] 0 0
Malopolskie
Country [61] 0 0
Poland
State/province [61] 0 0
Gdansk
Country [62] 0 0
Poland
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Poznan
Country [63] 0 0
Russian Federation
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Ekaterinburg
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Serbia
State/province [64] 0 0
Belgrade
Country [65] 0 0
Serbia
State/province [65] 0 0
Nis
Country [66] 0 0
Serbia
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Novi Sad
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Spain
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Navarra
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Spain
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Barcelona
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Spain
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Malaga
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Spain
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Sevilla
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Spain
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Valencia
Country [72] 0 0
Ukraine
State/province [72] 0 0
Dnipropetrovs'ka Oblast
Country [73] 0 0
Ukraine
State/province [73] 0 0
Ivano-Frankivsk
Country [74] 0 0
Ukraine
State/province [74] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04938427