A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
A Baseline-Controlled, Open-Label, Multicenter, Single-Arm, Pivotal Study to Evaluate the Efficacy, Safety, and Tolerability of NGN-401 in Subjects With Rett Syndrome (Embolden)
1 other identifier
interventional
33
3 countries
16
Brief Summary
This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jun 2023
Longer than P75 for phase_3
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 1, 2023
CompletedFirst Posted
Study publicly available on registry
June 12, 2023
CompletedStudy Start
First participant enrolled
June 13, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
March 13, 2026
March 1, 2026
6.5 years
June 1, 2023
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Efficacy of NGN-401
Responders will be defined as participants who: * Attain a CGI-I score of ≤ 3 ("minimally improved"); * and gain any one developmental milestone/skill from a list of 28, as captured through standardized video recordings and independently verified by blinded central raters.
52 Weeks
Study Arms (4)
Pediatric 1e15 vg dose (fully enrolled)
EXPERIMENTALDose Level 1 for ages 4-10 years
Adolescent/Adult 1e15 vg Dose (fully enrolled)
EXPERIMENTALDose Level 1 for ages 11 years \& above
Pediatric 3e15 vg dose (discontinued)
EXPERIMENTALDose Level 2 for ages 4-10 years (discontinued)
Pivotal Cohort
EXPERIMENTALDose Level 1 for ages 3 and above
Interventions
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.
Eligibility Criteria
You may qualify if:
- Females who are between the ages of ≥4 and ≤10 years for Arms 1 and 2 (Arms closed). Females who are ≥11 years of age or older for Arm 3 (Arm closed). Females who are ≥3 for Arm 4, the pivotal cohort.
- Diagnosis of typical Rett syndrome with a documented disease-causing mutation in the methyl-CpG-binding protein 2 (MECP2) gene
- Current anti-epileptic drug regimen has been stable for at least 12 weeks
- Participant must be in the post-regression stage
- Participant and caregiver should reside within a 2-hour drive of the study center for at least 3 months following treatment
- Participant must have never taken trofinetide or have taken trofinetide and discontinued due to tolerability, lack of efficacy, or other reasons. Following NGN-401 dosing, trofinetide may be initiated after a specified time period and with the support of the treating clinician.
You may not qualify if:
- Normal or near normal hand function
- Has a current clinically significant condition other than Rett syndrome
- Presence of a concomitant medical condition that precludes intracerebroventricular administration, or use of anesthetics or immune suppression needed for study related procedures
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Neurogene Inc.lead
Study Sites (16)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Nicklaus Children's Hospital Research Institute
Miami, Florida, 33155, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Kennedy Krieger Institute
Baltimore, Maryland, 21205, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Montefiore Medical Center
New York, New York, 10467, United States
UNC at Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
The Children's Hospital at Westmead
Sydney, New South Wales, Australia
Royal Hospital for Children and Young People
Edinburgh, EH16 4TJ, United Kingdom
Manchester University NHS Foundation Trust
Manchester, M13 9WL, United Kingdom
Related Publications (2)
Ross PD, Gadalla KKE, Thomson SR, Selfridge J, Bahey NG, Benito J, Burstein SR, McMinn R, Bolon B, Hector RD, Cobb SR. Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome. Sci Transl Med. 2025 Apr 2;17(792):eadq3614. doi: 10.1126/scitranslmed.adq3614. Epub 2025 Apr 2.
PMID: 40173263DERIVEDJagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159/000539267. Epub 2024 May 9.
PMID: 38723617DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Julie Jordan, MD
Neurogene Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Central raters for the acquisition of a developmental milestone/skill from videos are blinded to the intervention and to the timing of the video.
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 1, 2023
First Posted
June 12, 2023
Study Start
June 13, 2023
Primary Completion (Estimated)
December 1, 2029
Study Completion (Estimated)
December 1, 2029
Last Updated
March 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share