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Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies (ENVISION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04537832
Recruitment Status : Active, not recruiting
First Posted : September 3, 2020
Last Update Posted : May 16, 2022
Sponsor:
Information provided by (Responsible Party):
Encoded Therapeutics

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.

Condition or disease Intervention/treatment
Dravet Syndrome Other: No Intervention

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).

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Study Type : Observational
Actual Enrollment : 58 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ENVISION: Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies
Actual Study Start Date : January 18, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024


Group/Cohort Intervention/treatment
SCN1A-positive Dravet Syndrome
Participants aged between 6 and 60 months of age who have SCN1A-positive Dravet Syndrome. Clinical, neurocognitive, laboratory, the burden of disease, and health care resource utilization will be assessed.
Other: No Intervention
No Intervention




Primary Outcome Measures :
  1. Seizure burden [ Time Frame: Change from Baseline at 24 months ]
    Measured using monthly seizure frequency derived from seizure diaries.

  2. Seizure freedom [ Time Frame: Change from Baseline at 24 months ]
    Measured using the proportion of seizure-free days observed.

  3. Use of anti-seizure medication(s) [ Time Frame: Baseline through Month 24 ]
    Measured using the incidence of anti-seizure medication usage observed during the 60 days leading up to each nominal visit.

  4. Use of Special Diet [ Time Frame: 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.

  5. Cognitive functioning [ Time Frame: 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.


  6. Behavioral and social functioning [ Time Frame: 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


  7. Motor functioning [ Time Frame: 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.

  8. Incidence of Adverse Events [ Time Frame: Baseline through Month 24 ]
    Measured using the incidence of adverse events and serious adverse events (broken down by preferred term) observed during the study.

  9. Overall survival [ Time Frame: Baseline through Month 24 ]
    Measured using the incidence of death observed by a given time point during the study.


Biospecimen Retention:   Samples With DNA
Serum and Plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 60 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Infants and children aged between 6 and 60 months with SCN1A-positive Dravet Syndrome.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04537832


Locations
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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
UCSF Benioff Children's Hospital
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, New Jersey
Northeast Regional Epilepsy Group
Hackensack, New Jersey, United States, 07601
United States, Ohio
Abigail Wexner Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Le Bonheur Children's Hospital
Memphis, Tennessee, United States, 38103
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
United States, Washington
Multicare Institute for Research and Innovation
Tacoma, Washington, United States, 98405
Australia, Victoria
Austin Hospital - Melbourne Brain Centre
Heidelberg, Victoria, Australia, 3084
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Universitari i Politècnic La Fe
Valencia, Spain
United Kingdom
Queen Elizabeth Hospital
Glasgow, United Kingdom, G51 4TF
Sponsors and Collaborators
Encoded Therapeutics
Investigators
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Study Director: Salvador Rico, M.D., Ph.D Encoded Therapeutics
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Responsible Party: Encoded Therapeutics
ClinicalTrials.gov Identifier: NCT04537832    
Other Study ID Numbers: ETX-DS-001
First Posted: September 3, 2020    Key Record Dates
Last Update Posted: May 16, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Plan is undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Encoded Therapeutics:
severe myoclonic epilepsy
epilepsy
severe myoclonic epilepsy of infancy
SMEI
SCN1A related seizure disorder
epileptic encephalopathy
developmental and epileptic encephalopathies
DEE
Additional relevant MeSH terms:
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Brain Diseases
Epilepsy
Epilepsies, Myoclonic
Central Nervous System Diseases
Nervous System Diseases
Epilepsy, Generalized
Epileptic Syndromes