A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2024
• Main ID: NCT04938427
• Date of registration: 18/06/2021
• Prospective Registration: Yes
• Primary sponsor: Takeda
• 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)
• Date of first enrolment: November 8, 2021
• Target sample size: 270
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04938427
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Brazil, Canada, China, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Mexico, Netherlands, Poland, Russian Federation, Serbia, Spain, Ukraine, United States

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion 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.



Age minimum: 2 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Lennox Gastaut Syndrome (LGS)

Intervention(s)

Drug: Soticlestat

Drug: Placebo

Primary Outcome(s)

Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Maintenance Period (EMA Region Specific) [Time Frame: Baseline up to Week 16]

Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Full Treatment Period [Time Frame: Baseline up to Week 16]

Secondary Outcome(s)

CGI-I Seizure Intensity and Duration Score [Time Frame: Baseline up to Week 16]

Percent Change from Baseline in MMD Seizure Frequency per 28 Days During the Maintenance Period [Time Frame: Baseline up to Week 16]

Caregiver Global Impression of Improvement (Care GI-I) Score [Time Frame: Baseline up to Week 16]

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 [Time Frame: Baseline up to Week 16]

Number of Days When Rescue Antiseizure Medication (ASM) is Used [Time Frame: Baseline up to Week 16]

Percent Change From Baseline in Frequency of All Seizures per 28 Days During the Maintenance Period [Time Frame: Baseline up to Week 16]

Change From Baseline in Percentage of MMD Seizure-free Days [Time Frame: Baseline up to Week 16]

Change in Quality of Life Inventory-Disability (QI-Disability) Score [Time Frame: Baseline up to Week 16]

Percentage of Responders During the Maintenance Period [Time Frame: Baseline up to Week 16]

Longest MMD Seizure-free Interval [Time Frame: Baseline up to Week 16]

Percent Change from Baseline in Frequency of All Seizures per 28 Days During the Full Treatment Period [Time Frame: Baseline up to Week 16]

Clinical Global Impression of Improvement (CGI-I) Score [Time Frame: Baseline up to Week 16]

Percentage of Responders During the Full Treatment Period [Time Frame: Baseline up to Week 16]

CGI-I Nonseizure Symptoms Score [Time Frame: Baseline up to Week 16]

Secondary ID(s)

2021-002481-40

jRCT2051210073

TAK-935-3002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors