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