Current Environment:


This study will evaluate the safety profile of the investigational gene therapy, NGN-401, in female children with typical Rett syndrome.


Rett Syndrome

Recruitment Status


Detailed Description

The study is a phase 1/2, open-label study designed to assess the safety, tolerability, and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9), using Neurogene's proprietary transgene regulation technology. NGN-401 contains a full-length human MECP2 gene which is designed to express therapeutic levels of the MECP2 protein while avoiding overexpression. The study treatment will be administered under general anesthesia via intracerebroventricular (ICV) delivery. Each participant will be followed for safety and preliminary efficacy for 5 years after treatment and is expected to enroll in a long-term follow-up study for 10 years.

Eligibility Criteria

Inclusion Criteria:

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 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 needed for study related procedures
Grossly abnormal psychomotor development in the first 6 months of life
A history of other genetic disorders or neurological conditions, such as stroke, brain tumor, or autoimmune processes affecting the central nervous system

Other inclusion or exclusion criteria apply.


Intervention Type

Intervention Name




Phase 1, Phase 2



Min Age

4 Years

Max Age

10 Years

Download Date

March 13, 2024

Principal Investigator


Primary Contact Information

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For more information and to contact the study team:

A Novel, Regulated Gene Therapy (NGN-401) Study for Female Children With Rett Syndrome NCT05898620