A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome

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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Rett Syndrome Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System Intellectual Disability Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurodevelopmental Disorders Neurologic Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms X-Linked Intellectual Disability

Age range

3 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

The Children's Hospital at Westmead, Sydney, New South Wales, Australia

About this study

The pivotal study, Embolden (TM), is a conversion of the phase 1/2 study and is an open-label, baseline-controlled, multicenter, single-arm study designed to assess the efficacy, safety, and tolerability of administration of NGN401, an adeno-associated viral vector serotype 9 (AAV9) using Neurogene's proprietary transgene regulation technology. NGN-401 contains a full-length human MECP2 gene and is designed to express therapeutic levels of the MeCP2 protein while avoiding overexpression.

The study treatment will be given as a single administration under general anesthesia via intracerebroventricular (ICV) delivery. Each participant will be followed for efficacy and safety for 3 years after treatment, and is expected to enroll in a long-term follow-up study for 12 years.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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

Other inclusion and exclusion criteria apply.

Treatment and study plan

NGN-401

Genetic

NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.

Primary outcomes

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.

Sponsors and collaborators

Lead sponsor

Neurogene Inc.

Industry

Registry information

Official study title

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)

Important dates

Study start: 2023
Primary completion: 2029
Study completion: 2029
First posted: Jun 12, 2023
Registry last updated: Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Recruiting