A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome

Phase 2Active Not RecruitingNCT06283212

Encoded Therapeutics5 enrolled

Overview

EXPEDITION is a Phase 1/2 study in the UK to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet Syndrome aged 6 to \< 48 months. The study follows and open-label, dose-escalation design.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Dravet Syndrome

Interventions

ETX101DRUG

ETX101 is composed of a non-replicating, recombinant adeno-associated viral serotype 9 (rAAV9) vector used to deliver a GABAergic regulatory element (reGABA) and an engineered transcription factor that increases transcription of the SCN1A gene (eTFSCN1A)

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 47 Months

Medical Language ↔ Plain English

Inclusion Criteria: * Participant has a predicted loss of function pathogenic or likely pathogenic SCN1A variant * Participant must have experienced their first seizure between the age of 3 and 15 months * Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have high clinical suspicion of a diagnosis of Dravet syndrome * Participant is receiving at least one prophylactic antiseizure medication Exclusion Criteria: * Participant has another genetic mutation or clinical comorbidity which could potentially confound the typical Dravet phenotype * Participant has a known central nervous system structural and/or vascular abnormality (indicated by an MRI or CT scan of the brain). * Participant has an abnormality that may interfere with CSF distribution and/or has an existing ventriculoperitoneal shunt. * Participant is currently taking or has taken antiseizure medications (ASMs) at a therapeutic dose that are contraindicated in Dravet syndrome, including sodium channel blockers. * Participant has experienced seizure freedom for a period of 4 consecutive weeks within the 90-day period prior to informed consent. * Participant has previously received gene or cell therapy. * Participant is currently enrolled in a clinical trial or receiving an investigational therapy. * Participant has clinically significant underlying liver disease.

Locations (3)

Queen Elizabeth Hospital

Glasgow, United Kingdom

Great Ormond Street Hospital

London, United Kingdom

Sheffield Children's Hospital

Sheffield, United Kingdom

Outcomes

Primary Outcomes

Proportions of participants experiencing any treatment-emergent adverse events (AEs), serious adverse events (SAEs), related AEs, AEs with severity Grade ≥ 3, AEs resulting in study discontinuation, and AEs with fatal outcome.

Time frame: Day 1 through Study Completion, an average of 5 years

Change from baseline in the standard score of the Vineland Adaptive Behavior Scales - Third Edition Adaptive Behavior Composite at Week 52.

Time frame: Baseline to Week 52. Standard scores are normalized to a mean and SD of 100 and 15, respectively, and are not bounded by a range. Higher scores correspond to better outcomes.

Secondary Outcomes

Percent change in monthly countable seizure frequency (MCSF) to Week 52, with countable seizures defined as generalized tonic-clonic/clonic, focal motor with clearly observable clinical signs, tonic bilateral, and atonic seizures.

Time frame: Between the 8-week baseline period and the 48-week post-dosing assessment period (defined as Week 5 to Week 52 following administration of ETX101)

Change from baseline in the raw score of the Bayley Scales of Infant and Toddler Development® 4th Edition receptive language sub-domain at Week 52.

Time frame: Baseline to Week 52. Raw scores range from 0 to 49 and higher scores correspond to better outcomes.

Data from ClinicalTrials.gov

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