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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04938427




Registration number
NCT04938427
Ethics application status
Date submitted
18/06/2021
Date registered
24/06/2021
Date last updated
28/02/2024

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 - Soticlestat
Treatment: Drugs - Placebo

Experimental: Soticlestat - Participants weighing <45 kg: Soticlestat, mini-tablets, at the dose of 40 mg to 200 mg, orally or via gastrostomy tube (G-tube) or low-profile gastric tube (MIC-KEY button) or jejunostomy tube (J-tube), twice daily (BID) based on body weight up to 4 weeks in Titration Period. Participants will continue to receive the dose that they are on at the end of the titration period, for 12 weeks in the Maintenance Period. Total duration of the treatment will be up to 16 weeks (Treatment Period). Dose will be tapered down if participants decide 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 in Titration Period. Participants will continue to receive 300 mg BID for 12 weeks in the Maintenance Period. Total duration of the treatment will be up to 16 weeks (Treatment Period). Dose will be tapered down if participants decide to discontinue the treatment.

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 in the Titration Period. Participants will continue to receive the soticlestat placebo-matching mini-tablets or tablets for 12 weeks in the Maintenance Period. The total duration of the treatment will be up to 16 weeks (Treatment Period). Soticlestat matching tapering will be done to maintain the blind if participants decide to discontinue the treatment.


Treatment: Drugs: Soticlestat
Soticlestat mini-tablets or tablets.

Treatment: Drugs: Placebo
Soticlestat placebo-matching 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 up to Week 16
Primary outcome [2] 0 0
Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Maintenance Period (EMA Region Specific)
Timepoint [2] 0 0
Baseline up to Week 16
Secondary outcome [1] 0 0
Percentage of Responders During the Maintenance Period
Timepoint [1] 0 0
Baseline up to Week 16
Secondary outcome [2] 0 0
Percentage of Responders During the Full Treatment Period
Timepoint [2] 0 0
Baseline up to Week 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 in a Cumulative Response Curve
Timepoint [3] 0 0
Baseline up to Week 16
Secondary outcome [4] 0 0
Caregiver Global Impression of Improvement (Care GI-I) Score
Timepoint [4] 0 0
Baseline up to Week 16
Secondary outcome [5] 0 0
Clinical Global Impression of Improvement (CGI-I) Score
Timepoint [5] 0 0
Baseline up to Week 16
Secondary outcome [6] 0 0
CGI-I Nonseizure Symptoms Score
Timepoint [6] 0 0
Baseline up to Week 16
Secondary outcome [7] 0 0
Change in Quality of Life Inventory-Disability (QI-Disability) Score
Timepoint [7] 0 0
Baseline up to Week 16
Secondary outcome [8] 0 0
CGI-I Seizure Intensity and Duration Score
Timepoint [8] 0 0
Baseline up to 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 up to Week 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 up to Week 16
Secondary outcome [11] 0 0
Percent Change from Baseline in MMD Seizure Frequency per 28 Days During the Maintenance Period
Timepoint [11] 0 0
Baseline up to Week 16
Secondary outcome [12] 0 0
Change From Baseline in Percentage of MMD Seizure-free Days
Timepoint [12] 0 0
Baseline up to Week 16
Secondary outcome [13] 0 0
Longest MMD Seizure-free Interval
Timepoint [13] 0 0
Baseline up to Week 16
Secondary outcome [14] 0 0
Number of Days When Rescue Antiseizure Medication (ASM) is Used
Timepoint [14] 0 0
Baseline up to Week 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
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Oregon
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Pennsylvania
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South Carolina
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Texas
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Utah
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United States of America
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Washington
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Belgium
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Antwerpen
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Belgium
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Brabant Wallon
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Belgium
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Brussels
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Alberta
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British Columbia
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Ontario
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Beijing
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China
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Chongqing
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Hubei
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Nis
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Ivano-Frankivsk
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Kyiv

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

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04938427
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study 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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/ct2/show/NCT04938427