Lennox-Gastaut Syndrome (LGS)
Conditions
Interventions
Soticlestat or placebo will be available as yellow-red colored, film-coated
tablets and mini-tablets. The study drug (tablets/minitablets) can be swallowed
whole or can be crushed and mixed well in
Sponsors
Takeda
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Male or female and aged 2 to 35 years, inclusive, at the time of informed consent. • Documented clinical diagnosis of LGS supported by: - Onset of seizures usually between ages of 1 and 8 years. - Presence of multiple seizure types: including drop seizures (eg, tonic-atonic seizures) and other seizure types including atypical absence seizures, tonic-clonic, myoclonic, and partial seizures. - History of abnormal electroencephalogram (EEG) (eg, slow spike and wave [<2.5 Hz], slow or disorganized EEG background, generalized paroxysmal fast activity). - Developmental delay or intellectual disability consistent with LGS. • The participant has >=8 MMD seizures each month in the 3 months prior to screening based on the historical information and has >=8 MMD seizures per 28 days during the 4- to 6-week prospective baseline period. MMD seizures include: - Hemi-clonic or focal clonic. - Focal to bilateral tonic-clonic. - Generalized tonic-clonic. - Bilateral clonic. - Focal seizures with major motor signs (eg hypermotor seizures or involving major body areas such as lower extremities or trunk) leading to fall or likely fall. - Tonic seizures involving major body areas such as lower extremities or trunk leading to fall or likely fall. - Atonic seizures involving major body areas such as lower extremities or trunk leading to fall or likely fall. - Convulsive status. • Weighs >=10 kg at the screening visit (Visit 1). • Failure to control seizures despite appropriate trials of at least 1 ASMs based on historical information, and is currently on an anti-seizure therapy (eg, ASMs, vagus nerve stimulation, ketogenic/modified Atkins diet) or other treatment options considered as SOC. • 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. • Currently taking 0 to 3 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 counted as an ASM. ASM dosing regimen must remain constant throughout the study. • If on a diet, the subject's diet should be stable for 4 weeks before the screening visit; the subject should continue this diet throughout the duration of the study • Stable liver function • Female subjects of childbearing potential (defined as first menarche) must have a negative pregnancy test and agree to use an effective or highly effective method of birth control during the study and for 30 days following the last dose of study drug.
Exclusion criteria
Exclusion criteria: • Currently enrolled in a clinical study involving an investigational product (meaning not approved in that country other then soticlestat), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Note: compatibility will be determined based on consultation with the medical monitor or the sponsor. • Participated in a clinical study involving another study drug in the last 30 days (or 5 half-lives of the study drug, whichever is longer) before screening (Visit 1). • Received soticlestat in a previous clinical study. • Known hypersensitivity to any component of the soticlestat formulation. • 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 this study status epilepticus is defined as continuous seizure activity lasting longer than 5 minutes or repeated seizures without return to baseline in between seizures. • 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. • Any history of alcohol, opioid, or other drug use disorder, as per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, within the 2 years immediately before the screening(Visit 1). • Abnormal and clinically significant ECG abnormality at screening (Visit 1) or before randomization (Visit 2, including QT interval with Fridericia correction method (QTcF) >450 ms, confirmed with a repeat ECG using manual measurement of QTcF. Clinically significant ECG abnormalities should be discussed with medical monitor. • Abnormal clinical laboratory test results at screening (Visit 1) that suggest a clinically significant underlying disease that would compromise the well-being of the subject. If the subject has a serum alanine aminotransferase and/or aspartate aminotransferase level >2.5 times the upper limit of normal (ULN), the medical monitor should be consulted. • Currently pregnant or breastfeeding or is planning to become pregnant within 30 days of the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: • Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the full treatment period. For EMA registration: • Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the maintenance period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: To assess the following in subjects receiving soticlestat as compared with placebo during the full treatment period, unless otherwise noted: • Proportion of responders defined as those with >=50% reduction from baseline in MMD seizures during the maintenance period and the full treatment period. • Percent change from baseline in frequency of all seizures per 28 days during the maintenance period and the full treatment period. • Percent change from baseline in MMD seizure frequency per 28 days during the maintenance period. • Responder analysis of the proportion of subjects with | — |
Countries
Netherlands
Outcome results
None listed