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

NCT05419492 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ETX-DS-002
• Study Type: interventional
• Target: 47
• Locations: 3 countries
• Sites: 10

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.

Conditions

Dravet Syndrome

Keywords

Dravet; SCN1A; DEE; developmental and epileptic encephalopathy; Dravet Syndrome; SCN1A-positive; SCN1A+

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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).

Other Outcomes (3)

• 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.

  From Day 1 through Study Completion.

• Safety Endpoint: Proportion of participants experiencing SAEs leading to hospitalization.

  From Day 1 through Study Completion.

• Safety Endpoint: Overall survival.

  From Day 1 through Study Completion.

Study Arms (2)

Part 1 (US Only)

EXPERIMENTAL

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

Part 2

SHAM COMPARATOR

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

Interventions

ETX101 DRUG

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.

Part 1 (US Only); Part 2

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Encoded Therapeutics: lead

Study Sites (10)

UCSF Benioff Children's Hospitals

San Francisco, California, 94158, United States

RECRUITING

Colorado Children's Hospital

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Oregon Health and Science University (OSHU)

Portland, Oregon, 97239, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

The Royal Children's Hospital

Melbourne, Australia

RECRUITING

Queen Elizabeth Hospital

Glasgow, G51 4TF, United Kingdom

NOT YET RECRUITING

Great Ormond Street Hospital

London, WC1N3JH, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Epilepsies, Myoclonic; Generalized Epilepsy With Febrile Seizures Plus, Type 2

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Salvador Rico, M.D., Ph.D

  Encoded Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Encoded Patient Advocacy

CONTACT

+1 (650) 398-4301; patientadvocacy@encoded.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 15, 2022
• Study Start: May 14, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2033
• Last Updated: April 16, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); AU (1); GB (2)