Summary

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

Age: 3 Years and older

Gender: Female

Start Date: 06/13/2023

Primary Completion Date (Estimated): 12/01/2029

Study Completion Date (Estimated): 12/01/2029

Accepts Healthy Volunteers: No

Trial Purpose and 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

Age: 3 Years and older

Gender: Female

Accepts Healthy Volunteers: No

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.