Current Environment: Production

Summary

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

Conditions

Rett Syndrome

Recruitment Status

RECRUITING

Detailed Description

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.

Eligibility Criteria

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.

Intervention

Intervention Type

Intervention Name

GENETIC

NGN-401

Phase

PHASE3

Gender

FEMALE

Min Age

3 Years

Max Age

N/A

Download Date

2025-11-07

Principal Investigator

N/A

Primary Contact Information

Rett Research
rettresearch@childrens.harvard.edu

This field has been modified from ClinicalTrials.gov to show a contact specific to Boston Children's.

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team:

A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome NCT05898620 Rett Research rettresearch@childrens.harvard.edu