Dravet Syndrome, Epilepsy, SMEI Dravet Syndrome
Conditions
Interventions
None listed
Sponsors
Zogenix International Limited, a Wholly Owned Subsidiary of Zogenix, Inc.
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: 1. Subject is male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the Screening Visit. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine pregnancy test. Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control, which includes abstinence, while being treated on this study and for 90 days after the dose of study drug. 2. Subject must have documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs (AEDs). 3. Subjects must meet all of the following 5 criteria: a. Onset of seizures in the first year of life in an otherwise healthy infant. b. A history of seizures that are either generalized tonic-clonic or unilateral clonic or bilateral clonic, and are prolonged. c. Initial development is normal. d. History of normal brain magnetic resonance imaging (MRI) without cortical brain malformation. e. Lack of alternative diagnosis. 4. Subjects must meet at least one of the following 3 criteria: a. Emergence of another seizure type, including myoclonic, generalized tonic-clonic, tonic, atonic, absence and/or focal has developed after the first seizure type. b. Prolonged exposure to warm temperatures induces seizures and/or seizures are associated with fevers due to illness or vaccines, hot baths, high levels of activity and sudden temperature changes and/or seizures are induced by strong natural and/or fluorescent lighting, as well as certain visual patterns. c. Genetic test results consistent with a diagnosis of Dravet syndrome (pathogenic, likely pathogenic, variant of unknown significance, or inconclusive but unlikely to support an alternative diagnosis.) 5. Subject must have had *4 convulsive seizures (tonic-clonic, tonic, clonic) per 4-week period for past 12 weeks prior to screening, by parent/guardian report to investigator or investigator medical notes [Cohort 2 only]. 6. 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 screening and are expected to remain stable throughout the study. 7. Subject must be receiving a therapeutically relevant and stable dose of CLB, VPA, and STP for at least 4 weeks prior to screening and are expected to remain stable throughout the study [Cohort 2 only]. (In some cases, subjects who are conraindicated for VPA or CLB may be enrolled in Cohort 2. Subjects in these cases must be receiving a therapeutically relevant and stable dose of STP and VPA [if contraindicated for CLB] or STP and CLB [if contraindicated for VPA]. Each subject must be reviewed with the Medical Monitor and sponsor before initiating screening. The decision to allow enrollment of these subjects is at the sole discretion of the sponsor.) 8. Subject must be receiving a stable dose of CLB and VPA, administered twice daily (BID), to be eligible for Dose Regimen 1 and 2 or subject must be receiving a stable dose of CLB, VPA, and STP, administered BID, to be eligible for Dose Regimen 3 [Cohort 1 only]. 9. Subject agrees to provide a buccal swab sample for CYP2D6 (cytochrome P450 2D6) genotyping. 10. Subject has been informed of t
Exclusion criteria
Exclusion criteria: 1. Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication. 2. Subject has pulmonary arterial hypertension. 3. Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke. 4. Subject has current or recent history of anorexia nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month. 5. Subject has a current or past history of glaucoma. 6. Subject has moderate or severe hepatic impairment. a. Asymptomatic subjects with mild hepatic impairment (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint is the change in the mean convulsive seizure frequency (MCSF) per 28 days between the Baseline and T+M periods. The MCSF will be calculated from all available data collected during the Baseline or T+M Periods. The primary endpoint will be analyzed using an analysis of covariance (ANCOVA) model with treatment group (ZX008 or placebo) and age group ( | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary efficacy objectives of the study are related to Cohort 2 and include: To demonstrate that ZX008 is superior to placebo on the following endpoints: - The proportion of subjects who achieve a *40% reduction from baseline in convulsive seizure frequency. - The proportion of subjects who achieve a *50% reduction from baseline in convulsive seizure frequency. - The longest convulsive seizure-free interval. | — |
Countries
Netherlands
Outcome results
None listed