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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-13

Study Completion Date

2029-12-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Rett Syndrome

Keywords

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Typical Rett Syndrome MECP2 Rett Disorder Genetic Diseases, Inborn Genetic Diseases, X-Linked Neurodevelopmental Disorders Neurobehavioral Manifestations Neurologic Manifestations Intellectual Disability Nervous System Diseases Pathologic Processes RTT

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The study treatment will be delivered via intracerebroventricular (ICV) injection. All study participants will receive the same intervention.

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Central raters for the acquisition of a developmental milestone/skill from videos are blinded to the intervention and to the timing of the video.

Intervention Type GENETIC

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

Interventions

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NGN-401

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

Intervention Type GENETIC

Eligibility Criteria

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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

Minimum Eligible Age

3 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julie Jordan, MD

Role: STUDY_DIRECTOR

Neurogene Inc.

Manchester, , United Kingdom

Site Status TERMINATED

Countries

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United States Australia United Kingdom

Central Contacts

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Contact Center

Role: CONTACT

Phone: +1 877-237-5020

Email: [email protected]

Facility Contacts

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Role: primary

References

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Ross PD, Gadalla KKE, Thomson SR, Selfridge J, Bahey NG, Benito J, Burstein SR, McMinn R, Bolon B, Hector RD, Cobb SR. Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome. Sci Transl Med. 2025 Apr 2;17(792):eadq3614. doi: 10.1126/scitranslmed.adq3614. Epub 2025 Apr 2.

Reference Type DERIVED

PMID: 40173263 (View on PubMed)

Jagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159/000539267. Epub 2024 May 9.

Reference Type DERIVED

PMID: 38723617 (View on PubMed)

Other Identifiers

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RTT-200

Identifier Type: -

Identifier Source: org_study_id

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

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Pediatric 1e15 vg dose (fully enrolled)

NGN-401

Adolescent/Adult 1e15 vg Dose (fully enrolled)

NGN-401

Pediatric 3e15 vg dose (discontinued)

NGN-401

Pivotal Cohort

NGN-401

Interventions

NGN-401

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Neurogene Inc.

Responsible Party

Principal Investigators

Julie Jordan, MD

Locations

University of Alabama at Birmingham

UCSF Benioff Children's Hospital Oakland

Children's Hospital Colorado

Nicklaus Children's Hospital Research Institute

Rush University Medical Center

Kennedy Krieger Institute

Boston Children's Hospital

Montefiore Medical Center

UNC at Chapel Hill

Nationwide Children's Hospital

Vanderbilt University Medical Center

Texas Children's Hospital

The Children's Hospital at Westmead

Royal Hospital for Children and Young People

Manchester University NHS Foundation Trust

Countries

Central Contacts

Contact Center

Facility Contacts

References

Jagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159/000539267. Epub 2024 May 9.

Other Identifiers

RTT-200