A Study to Assess the Safety and Tolerability of ZX008 in Children and Young Adults With Dravet Syndrome or Lennox Gastaut Syndrome Currently Taking Cannabidiol

Study Overview
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Brief Summary
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This is an open label study to evaluate the safety of ZX008 (fenfluramine) in patients with Dravet syndrome (DS) or Lennox Gastaut syndrome (LGS) who are being administered cannabidiol (CBD).

Official Title
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An Open-Label Trial to Assess the Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Combination With Cannabidiol, as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome or Lennox-Gastaut Syndrome

Conditions
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Dravet Syndrome, Lennox Gastaut Syndrome

Intervention / Treatment
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* Drug: ZX008 0.2 to 0.8 mg/kg/day
* Drug: Cannabidiol


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject has a clinical diagnosis of DS or LGS, where convulsive seizures (generalized tonic clonic seizures, tonic seizures, atonic seizures, tonic/atonic seizures, focal seizures with clear observable motor signs) are not completely controlled by current AEDs. All medications or interventions for epilepsy (including ketogenic diet [KD] and vagal nerve stimulation [VNS]) must be stable for at least 4 weeks prior to first ZX008 dose and are expected to remain stable throughout the study. Subjects must be taking a stable dose of CBD for at least 4 weeks prior to first ZX008 dose. Subject's source of CBD is expected to be consistent for at least 3 months during study participation. Key Exclusion Criteria: Subject has current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke. Subject with current cardiac valvulopathy or pulmonary hypertension that the Investigator, parent/caregiver, Independent Cardiac Advisory Board, Independent Data and Safety Monitoring Committee, or sponsor deems clinically significant. Subject has a current or past history of glaucoma.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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: ZX008 0.2 to 0.8 mg/kg/day<br>ZX008 is supplied as an oral solution in a concentration of 2.5 mg/mL. Subjects will receive open-label ZX008 (flexible dosing 0.2 mg/kg/day to 0.8 mg/kg/day) | Drug: ZX008 0.2 to 0.8 mg/kg/day<br>* ZX008 drug is an oral aqueous solution of fenfluramine hydrochloride. The product is sugar free.<br>Drug: Cannabidiol<br>* Cannabidiol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of adverse events including serious adverse events, number of adverse events leading to study withdrawal | Baseline to Day 365 | 
| Change in Heart Rate | Change in resting heart rate using standard measures | Baseline to Day 365 | 
| Change in blood pressure | Change in resting blood pressure using standard measures | Baseline to Day 365 | 
| Change in temperature | Change in resting temperature using standard measures | Baseline to Day 365 | 
| Change in respiratory rate | Change in resting respiratory rate using standard measures | Baseline to Day 365 | 
| Changes in heart rhythm | Changes in heart beat as measured with 12-lead electrocardiogram | Baseline to Day 365 | 
| Changes in heart valve function | Changes in heart valves as measured with standard echocardiogram | Baseline to Day 365 | 
| Changes in treatment-emergent body weight and height | Changes in body weight and height by report of BMI in kg/m^2 | Baseline to Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dravet Syndrome, LGS