Clinical trial NCT06283212: A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome
Official title: EXPEDITION: 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
Lead sponsor: Encoded Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 4
Sex: ALL
Minimum age (years): 6
Maximum age (years): 47
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportions 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 fatal outcome.
timeFrame: Day 1 through Study Completion, an average of 5 years
measure: Change from baseline in the standard score of the Vineland Adaptive Behavior Scales - Third Edition Adaptive Behavior Composite at Week 52.
timeFrame: Baseline to Week 52. Standard scores are normalized to a mean and SD of 100 and 15, respectively, and are not bounded by a range. Higher scores correspond to better outcomes.
Secondary outcomes:
measure: Percent change in monthly countable seizure frequency (MCSF) to 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: Change from baseline in the raw score of the Bayley Scales of Infant and Toddler Development® 4th Edition receptive language sub-domain at Week 52.
timeFrame: Baseline to Week 52. Raw scores range from 0 to 49 and higher scores correspond to better outcomes.
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: Encoded Therapeutics
name: Salvador Rico, M.D., Ph. D
role: STUDY_DIRECTOR
References: