Dravet Syndrome
Conditions
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.
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 47 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change in monthly countable seizure frequency (MCSF) between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period. | Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52) |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in Bayley-4 cognitive subdomain raw score at Week 52 | Baseline to Week 52 |
| Change from Baseline in Vineland-3 subdomain GSVs at Week 52. | Baseline to Week 52. |
| Change from Baseline in Bayley-4 subdomain GSVs at Week 52. | Baseline to Week 52. |
| Proportion of participants achieving ≥ 75% reduction in MCSF between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period. | Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52). |
| Proportion of participants achieving ≥ 50% reduction in MCSF between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period. | Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52). |
| Change from Baseline in the Vineland-3 Adaptive Behavior Composite standard score at Week 52. | Baseline to Week 52. |
| Change from Baseline in Vineland-3 subdomain raw scores at Week 52. | Baseline to Week 52. |
| Change from Baseline in Bayley-4 subdomain raw scores (excluding cognitive subdomain) at Week 52. | Baseline to Week 52. |
| Proportion of CGI-I responders, defined as participants with a CGI-I score of 1 (Very much improved) or 2 (Much improved), at Week 52. | Baseline to Week 52. |
| Proportion of CGI-S responders, defined as participants who either have a CGI-S score of 1 (Normal, not at all ill) or demonstrate a ≥2 point improvement from Baseline, at Week 52. | Baseline to Week 52. |
Countries
United Kingdom
Contacts
STUDY_DIRECTORSalvador Rico, M.D., Ph. D
Encoded Therapeutics
Outcome results
None listed