Clinical trial NCT04537832: Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies
Official title: ENVISION: Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Dravet Syndrome
Keywords: severe myoclonic epilepsy
epilepsy
severe myoclonic epilepsy of infancy
SMEI
SCN1A related seizure disorder
epileptic encephalopathy
developmental and epileptic encephalopathies
DEE
Lead sponsor: Encoded Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-09-03
Enrollment: 58
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infants and children aged between 6 and 60 months with SCN1A-positive Dravet Syndrome.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Seizure burden
timeFrame: Change from Baseline at 24 months
measure: Seizure freedom
timeFrame: Change from Baseline at 24 months
measure: Use of anti-seizure medication(s)
timeFrame: Baseline through Month 24
measure: Use of Special Diet
timeFrame: Change from Baseline at 24 months
measure: Cognitive functioning
timeFrame: Change from Baseline at 24 months
measure: Behavioral and social functioning
timeFrame: Change from Baseline at 24 months
measure: Motor functioning
timeFrame: Baseline through Month 24
measure: Incidence of Adverse Events
timeFrame: Baseline through Month 24
measure: Overall survival
timeFrame: Baseline through Month 24
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Columbus
country: United States
facility: Abigail Wexner Research Institute at Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Tacoma
country: United States
facility: Multicare Institute for Research and Innovation
state: Washington
city: Heidelberg
country: Australia
facility: Austin Hospital - Melbourne Brain Centre
state: Victoria
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth Hospital
Study officials:
affiliation: Encoded Therapeutics
name: Salvador Rico, M.D., Ph.D
role: STUDY_DIRECTOR
References: