A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome
- Registration Number
- NCT06283212
- Lead Sponsor
- Encoded Therapeutics
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 4
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort Z ETX101 Cohort Z will evaluate ETX101 dose level 3. Cohort X ETX101 Cohort X will evaluate ETX101 dose level 1. Cohort Y ETX101 Cohort Y will evaluate ETX101 dose level 2.
- Primary Outcome Measures
Name Time Method 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. 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. 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 Outcome Measures
Name Time Method 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. 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. Baseline to Week 52. Raw scores range from 0 to 49 and higher scores correspond to better outcomes.
Trial Locations
- Locations (3)
Sheffield Children's Hospital
🇬🇧Sheffield, United Kingdom
Queen Elizabeth Hospital
🇬🇧Glasgow, United Kingdom
Great Ormond Street Hospital
🇬🇧London, United Kingdom