Clinical trial NCT06112275: 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)
Official title: WAYFINDER: a Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children with SCN1A-positive Dravet Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Dravet Syndrome
Keywords: Dravet
SCN1A
DEE
developmental and epileptic encephalopathy
Dravet Syndrome
SCN1A-positive
SCN1A+
Lead sponsor: Encoded Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-11-01
Enrollment: 4
Sex: ALL
Minimum age (years): 6
Maximum age (years): 83
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Day 1 through Study Completion, an average of 5 years
measure: 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.
timeFrame: 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)
measure: Proportion of participants free from episodes of prolonged seizures and/or status epilepticus at Week 52.
timeFrame: Week 5 through Week 52
Secondary outcomes:
measure: Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF) from Baseline at Week 52.
timeFrame: 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)
measure: Change from Baseline in the Vineland-Third Edition Expressive Communication raw score at Week 52.
timeFrame: Baseline through Week 52. Higher scores correspond to better outcomes.
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: The Royal Children's Hospital
Study officials:
affiliation: Encoded Therapeutics
name: Salvador Rico, M.D., Ph.D
role: STUDY_DIRECTOR
References: