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

Phase 1
Recruiting
Conditions
Dravet Syndrome
Interventions
Registration Number
NCT06112275
Lead Sponsor
Encoded Therapeutics
Brief Summary

WAYFINDER is a Phase 1/2 study in Australia to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged 6 to \<84 months. The study follows an open-label, dose-escalation design.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
4
Inclusion Criteria
  • Participant must have a predicted loss of function pathogenic or likely pathogenic SCN1A variant.
  • Participant must have experienced their first seizure between the ages of 3 and 15 months.
  • Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have a 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 6-month 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
GroupInterventionDescription
Cohort AETX101Cohort A will evaluate ETX101 dose level 1.
Cohort BETX101Cohort B will evaluate ETX101 dose level 2.
Cohort CETX101Cohort C will evaluate ETX101 dose level 3.
Cohort DETX101Cohort D will evaluate ETX101 dose level 4.
Primary Outcome Measures
NameTimeMethod
Percent change from Baseline in monthly countable seizure frequency (MCSF) at 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)
Proportion 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 a fatal outcome.Day 1 through Study Completion, an average of 5 years
Proportion of participants free from episodes of prolonged seizures and/or status epilepticus at Week 52.Week 5 through Week 52
Secondary Outcome Measures
NameTimeMethod
Change from Baseline in the Vineland-Third Edition Expressive Communication raw score at Week 52.Baseline through Week 52. Higher scores correspond to better outcomes.
Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF) from Baseline at Week 52.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)

Trial Locations

Locations (1)

The Royal Children's Hospital

🇦🇺

Melbourne, Australia

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