Dravet Syndrome
Conditions
Keywords
severe myoclonic epilepsy, epilepsy, severe myoclonic epilepsy of infancy, SMEI, SCN1A related seizure disorder, epileptic encephalopathy, developmental and epileptic encephalopathies, DEE
Brief summary
This is a multicenter, prospective, 2-year observational study in infants and children with developmental and epileptic encephalopathies (DEEs). The DEE currently being investigated is SCN1A-positive Dravet Syndrome.
Detailed description
This prospective, longitudinal, natural history master protocol has been designed to define the seizure, neurodevelopmental, and behavioral characteristics of SCN1A-positive Dravet Syndrome in infants and children between 6 and 60 months. It will also explore the impact of the disease on the participant's parent/caregiver quality of life (QoL) and healthcare resource utilization (HCRU).
Interventions
OTHERNo Intervention
No Intervention
Sponsors
Encoded Therapeutics
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to 60 Months
Healthy volunteers
No
Inclusion criteria
* Aged between 6 months and 60 months. * Confirmed SCN1A mutation. * Normal development prior to onset of first seizure as defined by the Centers for Disease -Control and Prevention (CDC 2019). * Onset of seizures between age 3 and 15 months, inclusive.
Exclusion criteria
* Copy number variant of SCN1A, including SCN1A microdeletion, if affecting other genes. * SCN1A mutation present on both alleles. * Known pathogenic or clinically suspected mutation in a seizure-associated gene besides SCN1A. * Confirmed mutation in a gene besides SCN1A that is known to increase the severity of the seizure phenotype. * Known gain-of-function genetic mutation, as defined by functional studies, including p.Thr226Met. * History of notable developmental deficit that was evident prior to seizure onset. * Known central nervous system structural abnormality as found on magnetic resonance imaging or computed tomography scan of brain. * Currently taking or has taken for 6 or more consecutive weeks anti-seizure medications (ASMs) at a therapeutic dose that are contraindicated in SCN1A-positive Dravet Syndrome, including sodium channel blockers. * Known concomitant genetic mutation or clinical comorbidity that potentially confounds typical Dravet phenotype.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seizure burden | Change from Baseline at 24 months | Measured using monthly seizure frequency derived from seizure diaries. |
| Seizure freedom | Change from Baseline at 24 months | Measured using the proportion of seizure-free days observed. |
| Use of anti-seizure medication(s) | Baseline through Month 24 | Measured using the incidence of anti-seizure medication usage observed during the 60 days leading up to each nominal visit. |
| Use of Special Diet | Change from Baseline at 24 months | Measured using the incidence of ketogenic/high-fat diet usage observed during the 60 days leading up to each nominal visit. |
| Cognitive functioning | Change from Baseline at 24 months | Measured using composite scores from 3 domains in the Bayley Scales of Infant and Toddler Development (3rd Edition) instrument. Domains include: (1) Cognitive; (2) Language; (3) Motor. Composite scores are normalized to a mean and SD of 100 and 15, respectively (range is not applicable as the scores are unbounded). Higher scores correspond to better outcomes compared to a normal population. |
| Behavioral and social functioning | Change from Baseline at 24 months | Measured using raw scores from 2 domains in the Brief Infant Toddler Social Emotional Assessment. Domains include: (1) Problem; and (2) Competence. Domain raw scores range from 31 to 93 and 11 to 33 for the Problem and Competence domains, respectively. Higher Problem scores correspond to worse outcomes. Higher Competence scores correspond to better outcomes |
| Motor functioning | Baseline through Month 24 | Measured using categorical outcomes of 7 motor items adapted from the Bayley Scales of Infant and Toddler Development instrument and NorthStar Ambulatory Assessment. Motor milestones include: (1) Sit unassisted for 30 seconds; (2) Walk with assistance; (3) Stand alone; (4) Walk alone; (5) Walk upstairs; (6) Run with Coordination; and (7)Jump forward. |
| Incidence of Adverse Events | Baseline through Month 24 | Measured using the incidence of adverse events and serious adverse events (broken down by preferred term) observed during the study. |
| Overall survival | Baseline through Month 24 | Measured using the incidence of death observed by a given time point during the study. |
Countries
Australia, Spain, United Kingdom, United States
Outcome results
None listed