NCT05898620

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)

Recruiting now Phase 3 Last updated 11 March 2026

What this trial tests

Phase 3 trial testing NGN-401 in Rett Syndrome in 33 participants. Currently enrolling.

Timeline

13 June 2023

Primary endpoint
1 December 2029

1 December 2029

Quick facts

Lead sponsor	Neurogene Inc.
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	single
Primary purpose	treatment
Enrollment	33
Start date	13 June 2023
Primary completion	1 December 2029
Estimated completion	1 December 2029
Sites	16 locations across United States, Australia, United Kingdom

Drugs / interventions tested

• NGN-401

Conditions studied

• Rett Syndrome — all drugs for Rett Syndrome →

Sponsor

Neurogene Inc. — full company profile →

Who can join

3 and older, female only, with Rett Syndrome. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Efficacy of NGN-401
  Time frame: 52 Weeks
  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.

Sponsor's own description

This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.
   Ye D, Chukwu C, Yang Y, Hu Z, et al · · 2024 · cited 24× · PMID 38906479 · DOI 10.1016/j.addr.2024.115363
2. Rett Syndrome: The Emerging Landscape of Treatment Strategies.
   Percy AK, Ananth A, Neul JL. · · 2024 · cited 20× · PMID 39251501 · DOI 10.1007/s40263-024-01106-y
3. Gene regulation technologies for gene and cell therapy.
   Butterfield GL, Reisman SJ, Iglesias N, Gersbach CA. · · 2025 · cited 17× · PMID 40195118 · DOI 10.1016/j.ymthe.2025.04.004
4. Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy.
   Jones DJ, Soundararajan D, Taylor NK, Aimiuwu OV, et al · · 2024 · cited 15× · PMID 39127888 · DOI 10.1016/j.ymthe.2024.08.009
5. Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.
   Słyk Ż, Stachowiak N, Małecki M. · · 2024 · cited 14× · PMID 39062095 · DOI 10.3390/biomedicines12071523
6. Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.
   Zhou L, Wang Y, Xu Y, Zhang Y, et al · · 2024 · cited 12× · PMID 39559557 · DOI 10.1016/j.omtm.2024.101357
7. Neurosurgical gene therapy for central nervous system diseases.
   Patel RV, Nanda P, Richardson RM. · · 2024 · cited 10× · PMID 39191071 · DOI 10.1016/j.neurot.2024.e00434
8. An Opportunity to Fill a Gap for Newborn Screening of Neurodevelopmental Disorders.
   Chung WK, Kanne SM, Hu Z. · · 2024 · cited 9× · PMID 38651398 · DOI 10.3390/ijns10020033