Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome

Study Overview
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Brief Summary
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To investigate the long-term safety and tolerability of clobazam when administered for 1 year as adjunctive therapy in paediatric patients aged ≥1 to ≤16 years with Dravet Syndrome.

Official Title
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Multi-site, Prospective, Open-label, Long-term, Flexible Dose, Interventional Study to Evaluate the Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome

Conditions
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Dravet Syndrome

Intervention / Treatment
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* Drug: Clobazam


Participation Criteria
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Eligibility Criteria
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The inclusion and exclusion criteria for the patients who participated in lead-in Study 14362A will be transferred from the 14362A study and for the patients who did not participate in lead-in Study 14362A the inclusion/exclusion is separately listed below. Inclusion Criteria: The patient has a diagnosis of Dravet Syndrome supported by: onset of seizures in the first year of life history of fever-induced prolonged seizures as determined by the Investigator these may include prolonged (approximately 15 minutes or longer) hemi-clonic seizures multiple seizure types which may include: generalised tonic-clonic (required for inclusion) clonic (required for inclusion) myoclonic jerks/seizures history of normal development prior to seizure onset followed by development delay or regression after seizure onset abnormal EEG consistent with Dravet Syndrome The patient is currently receiving a stable dose of clobazam of at least 0.5 mg/kg/day (maximum 20 mg/day) for at least 3 months Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clobazam<br>A maximum of 2.0 mg/kg/day (maximum 80 mg/day) twice daily (BID); clobazam oral suspension (2.5 mg/mL) or clobazam scored tablets (10 mg), orally | Drug: Clobazam<br> <br> * Other names: Onfi®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability |  | Up to Day 390 | 
| Number of Participants With Adverse Events of Special Interest as a Measure of Safety and Tolerability Based on Dose |  | Up to Day 390 | 
| Columbia Suicide Severity Rating Scale (C-SSRS), Categorisation Based on Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories (1, 2, 3, 4 and 7) for Patients Aged ≥ 6 Years |  | Baseline and from Day 0 to Day 360 | 
| Change in Behavioural, Neurocognitive Measures Using Vineland Adaptive Behaviour Scale (VABS) |  | Baseline and from Day 0 to Day 360 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Weekly Number of Tonic-clonic and Clonic Seizures |  | Baseline and from Day 0 to Day 360 and upon Study Completion/Withdrawal | 
| Number of Initial Treatment Responders Who Returned to Their Baseline Tonic-clonic and Clonic Seizure Rate During the Study (an Assessment of Tachyphylaxis) |  | Baseline and from Day 0 to Day 360 | 
| Percentage of Initial Treatment Responders Who Returned to Their Baseline Tonic-clonic and Clonic Seizure Rate During the Study (an Assessment of Tachyphylaxis) |  | Baseline and from Day 0 to Day 360 |