Dravet Syndrome
Conditions
Keywords
Dravet, SCN1A, DEE, developmental and epileptic encephalopathy, Dravet Syndrome, SCN1A-positive, SCN1A+
Brief summary
ENDEAVOR is a Phase 1/2, 2-part, multicenter study to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged ≥6 to \<36 months (Part 1A), aged ≥48 months to \<18 years (Part 1B), and aged ≥6 to \<48 months (Part 2). Part 1A follows an open-label, dose-escalation design, Part 1B follows an open-label design, and Part 2 is a randomized, double-blind, sham delayed-treatment control study.
Interventions
DRUGETX101
ETX101 is a non-replicating, recombinant adeno-associated viral vector serotype 9 (rAAV9) comprising a GABAergic regulatory element (reGABA) and an engineered transcription factor that increases transcription of the SCN1A gene (eTFSCN1A). ETX101 is intended as a one-time intracerebroventricular (ICV) administration.
Sponsors
Encoded Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1A and Part 1B are open-label with no blinding. Part 2 will be conducted in a double-blinded manner whereby all Primary Site Staff (including clinicians, research coordinators, neuropsychologists, pharmacists, and physical therapists), study participants and caregivers, Sponsor and Sponsor-designees will be blinded through the end of Week 52 following Day 1 for each participant. The Surgical Site Staff will be unblinded to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be aged between ≥6 months and \<36 months in Part 1A, ≥48 months and \<18 years in Part 1B, ≥6 months and \<48 months in Part 2. * 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 has received sodium channel blockers during the Pre-Dosing Seizure Period. * 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 (Key Secondary Endpoint for Part 2). | From Baseline to Week 52. |
| Change from Baseline in Vineland-3 subdomain GSVs at Week 52. | From Baseline to Week 52. |
| Change from Baseline in Bayley-4 subdomain GSVs at Week 52. | From 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. | From Baseline to Week 52. |
| Change from Baseline in Vineland-3 subdomain raw scores at Week 52. | From Baseline to Week 52. |
| Change from Baseline in Bayley-4 subdomain raw scores (excluding cognitive subdomain) at Week 52. | From 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. | From 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. | From Baseline to Week 52. |
Countries
Australia, United Kingdom, United States
Contacts
CONTACTEncoded Patient Advocacy
STUDY_DIRECTORSalvador Rico, M.D., Ph.D
Encoded Therapeutics
Outcome results
None listed