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

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

Detailed Description
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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.

Official Title
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A Phase 1/2, Open-Label Clinical Study to Evaluate Safety, Tolerability, and Efficacy of NGN-401 in Pediatric Subjects With Rett Syndrome

Conditions
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Rett Syndrome

Intervention / Treatment
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* Genetic: NGN-401


Participation Criteria
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Eligibility Criteria
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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 must 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.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants will receive a single intracerebroventricular (ICV) administration of the study treatment. | Genetic: NGN-401<br>* NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Incidence, type, severity, and frequency of TEAEs | 5 years | 
| Incidence of Serious Adverse Events (SAEs) | Incidence, type, severity, and frequency of SAEs | 5 years | 
| Incidence of Adverse Events of Special Interest (AESIs) | Incidence, type, severity, and frequency of AESIs | 5 years | 
| Incidence of clinical laboratory abnormalities | Incidence, type, severity, and frequency of clinical laboratory abnormalities | 5 years | 
| Incidence of new physical and neurologic exam abnormalities | Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, Heredodegenerative Disorders, Nervous System, Pathologic Processes, RTT