Natural History Study in Pediatric Patients With STXBP1 Encephalopathy With Epilepsy

Study Overview
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Brief Summary
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This is a prospective, non-interventional, longitudinal study designed to characterize the natural history of STXBP1 related encephalopathy with epilepsy, in participants ≤ <5 years of age.

Official Title
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A Phase 0 Non-interventional, Multi-center, Natural History Study in Pediatric Patients With Syntaxin Binding Protein 1 (STXBP1) Encephalopathy With Epilepsy

Conditions
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STXBP1 Encephalopathy With Epilepsy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, > 1 day to ≤ 5 years of age at the time of informed consent. Diagnosed with seizure disorder Presence of a STXBP1 gene mutation. Historical documentation is sufficient to support eligibility for the study. Confirmatory testing will be obtained at baseline and performed by a CLIA certified laboratory Written informed consent provided by a parent or legal guardian Exclusion Criteria: History of prior gene therapy treatment Current enrollment in an interventional study or has received an investigational drug within 30 days or fewer than 5 half-lives prior to screening visit, whichever is longer Treatment with any antisense oligonucleotide therapy within 6 months prior to screening and anticipate remaining on treatment throughout the study The presence of a confirmed mutation in a gene other than STXPB1 that is known to contribute to a neurodevelopmental disability Presence of a significant non-STXBP1 related central nervous impairment/behavioral disturbance that would confound the scientific rigor or interpretation of results of the study History of prematurity (defined as gestational age <35 weeks), interventricular hemorrhage, structural brain deficit or congenital heart disease Requires mechanical ventilation or non-invasive respiratory support such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) at the time of informed consent

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in neurodevelopmental parameters of adaptive behavior function over time utilizing the Vineland Adaptive Behavior Scales-II (VABS-II) Age-equivalent Scores | The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. | 2 Years | 
| Changes in neurodevelopment parameters over time utilizing an age appropriate assessment. | The determination of whether a patient received Bayley Scales of Infant Development-III (BSID-III) is based on an algorithm that includes the patient's calendar age and VABS-II age-equivalent score (See Outcome 1). The BSID-III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. contains two scoring systems of composite scores and percentile ranks. The normal range for composite scores is between 40-160 with mean at 100 and 0-99 for the percentile ranks. Higher scores mean a better outcome. | 2 Years | 
| Changes in neurodevelopment parameters over time utilizing an age appropriate assessment. | The determination of whether a patient received Kaufman Assessment Battery for Children-II (KABC-II) is based on an algorithm that includes the patient's calendar age and VABS-II age-equivalent score (See Outcome 1). The KABC-II is an individually administered measure of processing and reasoning abilities. The scoring range is 69 and below through 131 or greater. Higher scores mean a better outcome. | 2 Years | 
| Changes in seizure frequency over time | Seizure diary | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in communication ability over time | Observer-Reported Communication Ability (ORCA) Outcome Measure. The ORCA measure produces a single score that is an estimate of an individual's overall level of communication ability. Higher ORCA scores reflect greater communication ability; the mastery of expressive, receptive, and pragmatic types of communication and higher vocabularies for verbal words and symbols on assistive devices. The ORCA T-score range is from 26.82 to 83.24. | 2 Years | 
| Changes in sleep behavior over time | Patient sleep habits will be assessed using Children's Sleep Habits Questionnaires (CSHQ). | 2 Years | 
| Changes in electroencephalogram (EEG) recording over time | Standard EEG, lasting approximately 1 hour, to assess the presence of epileptiform activity. | 2 Years | 
| Changes in motor function over time utilizing an age appropriate assessment. | The Hammersmith Infant Neurological Examination (HINE) is aimed to be used for infants between 3 and 24 months of age and assess different aspects of neurological function: cranial nerve function, movements, reflexes and protective reactions and behavior, as well as some age-dependent items that reflect the development of gross and fine motor function. Each item is scored 0-3, higher scores mean a better outcome. | 2 Years | 
| Changes in motor function over time utilizing an age appropriate assessment. | The Gross Motor Function Measure-88 is aimed to be used for children 5 months or older of age and assess changes in gross motor function over time. Each item is scored 0-3, higher scores mean a better outcome. | 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STXBP1, Epilepsy, Seizures, Epileptic encephalopathy, Genetic Diseases, Inborn