E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lennox-Gastaut Syndrome (LGS) |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048816 |
E.1.2 | Term | Lennox-Gastaut syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on therapy to standard of care (SOC) as compared with placebo during the full treatment period (titration + maintenance).
For European Medicines Agency (EMA) registration: - To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on therapy to SOC compared with placebo during the maintenance period only. |
|
E.2.2 | Secondary objectives of the trial |
To assess the following in subjects taking soticlestat as compared with placebo during the full treatment period, unless otherwise noted: - Proportion of treatment responders defined as those with ≥50% reduction in MMD seizures from baseline during the maintenance period and the full treatment period. -Effect on total seizure frequency of all seizure types during the maintenance period and the full treatment period. - Change from baseline in proportion of MMD seizure-free days. - Longest MMD seizure-free interval. - Number of days when rescue ASMs are used. - Effect on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (Care GI-I). - Effect on CGI-I Seizure Intensity and Duration. - Effect on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregiver. - Effect on Quality of Life Inventory-Disability (QI-Disability). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- 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 European Medicines Agency (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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary end points will be assessed throughout the study. |
|
E.5.2 | Secondary end point(s) |
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. - Responder analysis of the proportion of subjects with ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% reduction from baseline in MMD seizures in a cumulative response curve. - Care GI-I (caregiver). - CGI-I (clinician). - CGI-I Nonseizure Symptoms. - Change in QI-Disability score. - CGI-I Seizure Intensity and Duration. - 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. - Change from baseline in proportion of MMD seizure-free days. - Longest MMD seizure-free interval. - Number of days when rescue ASM is used. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be assessed throughout the study. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Australia |
Brazil |
Canada |
China |
Japan |
Mexico |
Russian Federation |
Serbia |
United Kingdom |
United States |
Belgium |
France |
Germany |
Greece |
Hungary |
Italy |
Latvia |
Netherlands |
Poland |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study for an individual subject who does not enroll in the OLE study on the same day as Visit 11/early termination is either: - The day of the scheduled safety follow-up phone call or visit. OR -Midnight of the day after Visit 11/early termination but before the scheduled safety follow-up phone call. The end of study for an individual subject who enrolls in the OLE study on the same day as Visit 11/early termination is midnight of that same day. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 10 |