E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dravet Syndrome (DS) Lennox-Gastaut Syndrome (LGS) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073682 |
E.1.2 | Term | Dravet syndrome |
E.1.2 | System Organ Class | 100000004850 |
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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 |
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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 long-term safety and tolerability of soticlestat when administered as adjunctive therapy to SOC (eg, ASMs, vagus nerve stimulation, ketogenic diet, modified Atkins diet) in subjects with DS or LGS. |
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E.2.2 | Secondary objectives of the trial |
- To assess the effect of soticlestat on seizure frequency (convulsive seizures for the DS cohort, MMD seizures for the LGS cohort, and total seizure count for each cohort). - To assess the effect of soticlestat on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (Care GI-I). - To assess the effect of soticlestat on CGI-I Seizure Intensity and Duration. - To assess the effect of soticlestat on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregiver. - To assess the effect on Quality of Life Inventory-Disability (QI-Disability). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject must have: Been previously enrolled in a phase 3 soticlestat clinical study.
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E.4 | Principal exclusion criteria |
1. 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. 2. Abnormal and clinically significant ECG abnormality at Visit 1 including QT interval with Fridericia correction method (QTcF) >450 ms confirmed with a repeat ECG using manual measurement of QTcF. 3. Participant is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. Particpants who have positive answers on item numbers 4 or 5 on the CSSRS before dosing are excluded. This scale will only be administered to subjects aged ≥6 years. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence of TEAEs. - Incidence of abnormal values for clinical laboratory tests and electrocardiogram (ECG) evaluations. - Change from baseline in clinical laboratory test values, vital signs and Columbia-Suicide Severity Rating Scale (C-SSRS), and ECG parameters. - Change from baseline in height and weight for all age groups. - Absolute value for Tanner stage for children 6 to 17 years of age during the study. - Absolute values for IGF-1 for children 2 to 17 years of age during the study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary end points will be assessed throughout the study. |
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E.5.2 | Secondary end point(s) |
- Percent change from baseline in total seizure frequency per 28 days for each (DS and LGS) cohort. - Percent change from baseline in convulsive seizure frequency (DS) per 28 days. - Percent change from baseline in MMD seizure frequency (LGS) per 28 days. - Effect on the CGI-I and 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 caregivers. - Effect on QI-Disability. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be assessed throughout the study. |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Australia |
Brazil |
Canada |
China |
Japan |
Mexico |
United States |
Russian Federation |
Ukraine |
Serbia |
Belgium |
France |
Germany |
Greece |
Hungary |
Italy |
Latvia |
Netherlands |
Poland |
Spain |
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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
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The end of the study for an individual subject is defined as the last protocol-specified contact with that subject. The overall end of the study is defined as the last protocol-specified contact with the last subject ongoing in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |