Continuous Spike and Waves During Slow Sleep, Inv Dup(15) Encephalopathy, Multifocal or Bilateral Malformations of Cortical Development, Refractory Epilepsy, STXBP1 Encephalopathy With Epilepsy, SYNGAP1 Encephalopathy
Conditions
Keywords
refractory epilepsy, SYNGAP1, STXBP1, Inv Dup(15), developmental and epileptic encephalopathies, DEEs, Epilepsy, Drug Resistant Epilepsy, Intractable epilepsy, Nervous System Diseases, Genetic Diseases, Inborn
Brief summary
This study is a pilot non-controlled clinical trial with adjunctive fenfluramine for the treatment of five different types of developmental and epileptic encephalopathies (DEEs) focused on epileptic and non-epileptic outcomes: SYNGAP1 and STXBP1 encephalopathies, inv-dup(15) encephalopathy, multifocal or bilateral malformations of cortical development, and continuous spikes and waves during sleep. The main goal is to assess changes in seizure frequency comparing before and after treatment with fenfluramine in five specific types of developmental and epileptic encephalopathies (DEEs). Secondary objectives of this study are the analysis of changes in seizure intensity and duration, and non-epileptic outcomes such as variations in cognitive activity, level of alertness, impulsivity/self-control, gait stability and other alterations that might be detected during the interview and physical examination.
Interventions
DRUGFenfluramine
Administration of fenfluramine. Fenfluramine treatment dose: Between 0.2 and 0.7 mg/kg/day if no concomitant Stiripentol (STP), maximum dose: 40 mg/day \[or 0.5 mg/kg/day, maximum 30 mg/day, for subjects taking concomitant STP\]. Dosing will be started with 0.1mg/day per one week, then 0.2mg/kg/day per one week, then as investigator clinical decision-making, up to 0.4, 0.6 or 0.7mg/kg/day, with a maximum of 0.2mg/kg/day escalation every week. Visits: There will be four visits; (visit 1) screening; (visit 2) treatment initiation, +2 weeks; (visit 3, telematic) +8 weeks; (visit 4) +14 weeks.
Sponsors
Zogenix, Inc.
Hospital Ruber Internacional
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
4 Group Assignment
Eligibility
Sex/Gender
ALL
Age
2 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
GENERAL INCLUSION CRITERIA: * Age between 2 and 35 years (both included). * Diagnosis of epilepsy associated with some degree of intellectual disability, starting before 11 years of age. * All patients will have a phenotype consistent with their genetic, electroclinical or neuroimaging diagnosis. SPECIFIC INCLUSION CRITERIA PER GROUP: ---GROUP 1: Non-controlled epilepsy after failing at least 3 antiseizure medications, with a minimum of 4 countable seizures with motor semiology per month during the baseline period of 3 months. * Group 1A: Patients with genetic testing showing a pathogenic or likely pathogenic variant in main synaptopathy genes (SYNGAP1 and STXBP1). * Group 1B: Patients with genetic testing showing a pathogenic or likely pathogenic inverted duplication of chromosome 15 \[inv-dup (15)\]. * Group 1C: Patients with neuroimaging showing multifocal or bilateral malformations of cortical development. * GROUP 2: Electroclinical diagnosis of Continuous Spikes and Waves during Sleep (CSWS) syndrome, with baseline video-EEG monitoring showing epileptiform activity occupying at least 50% of slow sleep tracing, after failing at least 3 antiseizure medications. ADDITIONAL INCLUSION CRITERIA: In addition, all subjects must meet all of the following inclusion criteria to be enrolled into the study: * Subject is male or non-pregnant, non-lactating female. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening and during the study. * Receiving at least 1 concomitant antiseizure medications (ASMs) and up to 4 concomitant ASMs, inclusive. Ketogenic Diet (KD) and Vagus Nerve Stimulation (VNS) are permitted but do not count towards the total number of ASMs. Rescue medications for seizures are not counted towards the total number of ASMs. * All medications or interventions for epilepsy (including ketogenic diet and vagal nerve stimulation) must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study. * Subject has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian. * Subject has provided assent in accordance with Institutional Review Board (IRB)/Ethics Committee requirements, if capable. * Subject's parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seizure frequency. | 12 months. | Seizure diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Behaviour. | 12 months. | Behaviour Rating Inventory of Executive Function. |
| Gross motor function. | 12 months. | Gross Motor Function Measure (GMFM). |
| Sleep habits. | 12 months. | Parent-reported Children's Sleep Habits Questionnaire. |
| Seizure severity. | 12 months. | Chalfont Seizure Severity Scale (CSSS). |
| Quality of life and family impact. | 12 months. | PedsQL 4.0. |
| Epileptiform activity | 12 months. | 12h video-EEG monitoring. |
| Global impression of change. | 12 months. | Caregiver Global Impression of Change. |
Countries
Spain
Contacts
Primary ContactAna Rodriguez
Outcome results
None listed