A Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children with SCN1A-Positive Dravet Syndrome
- Registration Number
- NCT05419492
- Lead Sponsor
- Encoded Therapeutics
- 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 1) and aged ≥6 to \<48 months (Part 2). Part 1 follows an open-label, dose-escalation design, and Part 2 is a randomized, double-blind, sham delayed-treatment control, dose-selection study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 22
Inclusion Criteria
- Participant must be aged between ≥6 months and <36 months in Part 1 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 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, including under an expanded access and/or compassionate use program.
- Participant has clinically significant underlying liver disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 ETX101 Part 1 will follow an open-label, rule-based, dose-escalation design and will evaluate up to 4 dose levels of ETX101. Part 2 ETX101 Part 2 is a dose-selection study, which will follow a double-blind (up through Week 52), randomized, sham delayed-treatment control design. There will be up to 3 cohorts in Part 2. If it is determined two dose levels of ETX101 will be evaluated in Part 2, participants will be randomized 1:1:1 to study treatment or sham procedure with delayed treatment. If Part 2 proceeds with a single dose level of ETX101, participants will be randomized 2:1 to study treatment or sham procedure with delayed treatment.
- Primary Outcome Measures
Name Time Method 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 a fatal outcome. Day 1 through Study Completion Percent change in monthly countable seizure frequency (MCSF) period, with countable seizures defined as generalized tonic-clonic/clonic, focal motor with clearly observable clinical signs, tonic, or atonic seizures. Between the pre-dose period (Part 1: 30 days prior to consent and the collection period through Day -1; Part 2: collection period between Day -72 and Day -1) and the 48-week post dosing period (defined as Week 5 through Week 52)
- Secondary Outcome Measures
Name Time Method Absolute change in monthly countable seizure frequency (MCSF) Between the pre-dose period (Part 1: 30 days prior to consent and the collection period through Day -1; Part 2: collection period between Day -72 and Day -1) and the 48-week post dosing period (defined as Week 5 through Week 52) Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF). Between the pre-dose period (Part 1: 30 days prior to consent and the collection period through Day -1; Part 2: collection period between Day -72 and Day -1) and the 48-week post dosing period (defined as Week 5 through Week 52) Change from baseline in the Vineland-3 Expressive Communication raw score at Week 52 Baseline through Week 52
Trial Locations
- Locations (3)
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
UCSF Benioff Children's Hospitals
🇺🇸San Francisco, California, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States