Dravet Syndrome
Conditions
Keywords
Dravet, SCN1A, DEE, developmental and epileptic encephalopathy, Dravet Syndrome, SCN1A-positive, SCN1A+
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.
Interventions
DRUGETX101
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).
Sponsors
Encoded Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 83 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 free from episodes of prolonged seizures and/or status epilepticus at Week 52. | Week 5 through Week 52 |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| 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. |
Countries
Australia
Outcome results
None listed