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

March 11, 2026 updated by: Neurogene Inc.

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

33

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia
        • Active, not recruiting
        • The Children's Hospital at Westmead
  • United Kingdom
      • Edinburgh, United Kingdom, EH16 4TJ
        • Terminated
        • Royal Hospital for Children and Young People
      • Manchester, United Kingdom, M13 9WL
        • Terminated
        • Manchester University NHS Foundation Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
    • California
      • Oakland, California, United States, 94609
    • Colorado
    • Florida
      • Miami, Florida, United States, 33155
    • Illinois
      • Chicago, Illinois, United States, 60612
    • Maryland
    • Massachusetts
    • New York
      • New York, New York, United States, 10467
    • North Carolina
    • Ohio
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Not yet recruiting
        • Children's Hospital of Philadelphia
    • Tennessee
      • Nashville, Tennessee, United States, 37232
    • Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pediatric 3e15 vg dose (discontinued)
Dose Level 2 for ages 4-10 years (discontinued)
Genetic: NGN-401
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.
Experimental: Pediatric 1e15 vg dose (fully enrolled)
Dose Level 1 for ages 4-10 years
Genetic: NGN-401
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.
Experimental: Adolescent/Adult 1e15 vg Dose (fully enrolled)
Dose Level 1 for ages 11 years & above
Genetic: NGN-401
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.
Experimental: Pivotal Cohort
Dose Level 1 for ages 3 and above
Genetic: NGN-401
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
52 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neurogene Inc.

Investigators

  • Study Director: Julie Jordan, MD, Neurogene Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2023

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

June 1, 2023

First Submitted That Met QC Criteria

June 1, 2023

First Posted (Actual)

June 12, 2023

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTT-200

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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