A Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children With SCN1A-Positive Dravet Syndrome (ENDEAVOR)

June 2, 2026 updated by: Encoded Therapeutics

ENDEAVOR: A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Infants and Children With SCN1A-Positive Dravet Syndrome

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

47

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Melbourne, Australia
        • Recruiting
        • The Royal Children's Hospital
        • Contact:
          • Prof. Ingrid Scheffer
        • Contact:
          • Dr. Katherine Howell
  • United Kingdom
      • Glasgow, United Kingdom, G51 4TF
      • London, United Kingdom, WC1N3JH
  • United States
    • California
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Benioff Children's Hospitals
        • Contact:
        • Principal Investigator:
          • Adam Numis
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Florida
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Contact:
        • Principal Investigator:
          • Linda Laux
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Not yet recruiting
        • Mott Children's Hospital
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Not yet recruiting
        • Mayo Clinic
        • Contact:
    • Ohio
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University (OSHU)
        • Contact:
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • Cook Children's Medical Center
        • Contact:
        • Principal Investigator:
          • Scott Perry

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 5 months (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 (US Only)
Part 1A will follow an open-label, rule-based, dose-escalation design and will evaluate up to 4 dose levels of ETX101. Part 1B will follow an open-label design and will evaluate 1 dose level of ETX101.
Drug: ETX101
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.
Sham Comparator: Part 2

Part 2 will follow a double-blind (up through Week 52), randomized, sham delayed-treatment control design.

There will be 2 cohorts in Part 2. A single dose level of ETX101 will be evaluated in Part 2 and participants will be randomized 2:1 to study treatment or sham procedure with delayed treatment.
Drug: ETX101
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent change in monthly countable seizure frequency (MCSF) between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period.
Time Frame: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).
Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Bayley-4 cognitive subdomain raw score at Week 52 (Key Secondary Endpoint for Part 2).
Time Frame: From Baseline to Week 52.
From Baseline to Week 52.
Change from Baseline in Vineland-3 subdomain GSVs at Week 52.
Time Frame: From Baseline to Week 52.
From Baseline to Week 52.
Change from Baseline in Bayley-4 subdomain GSVs at Week 52.
Time Frame: From Baseline to 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.
Time Frame: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).
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.
Time Frame: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).
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.
Time Frame: From Baseline to Week 52.
From Baseline to Week 52.
Change from Baseline in Vineland-3 subdomain raw scores at Week 52.
Time Frame: From Baseline to Week 52.
From Baseline to Week 52.
Change from Baseline in Bayley-4 subdomain raw scores (excluding cognitive subdomain) at Week 52.
Time Frame: From Baseline to 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.
Time Frame: From Baseline to 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.
Time Frame: From Baseline to Week 52.
From Baseline to Week 52.

Other Outcome Measures

Outcome Measure
Time Frame
Safety Endpoint: Proportions of participants experiencing any treatment-emergent DLTs (for Part 1A only), AEs, serious adverse events (SAEs), related AEs, AEs with severity Grade ≥ 3, AEs resulting in study discontinuation, and AEs resulting in death.
Time Frame: From Day 1 through Study Completion.
From Day 1 through Study Completion.
Safety Endpoint: Proportion of participants experiencing SAEs leading to hospitalization.
Time Frame: From Day 1 through Study Completion.
From Day 1 through Study Completion.
Safety Endpoint: Overall survival.
Time Frame: From Day 1 through Study Completion.
From Day 1 through Study Completion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Encoded Therapeutics

Investigators

  • Study Director: Salvador Rico, M.D., Ph.D, Encoded Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2024

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2033

Study Registration Dates

First Submitted

June 10, 2022

First Submitted That Met QC Criteria

June 10, 2022

First Posted (Actual)

June 15, 2022

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ETX-DS-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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