A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
- Conditions
- Rett Syndrome
- Interventions
- Genetic: NGN-401
- Registration Number
- NCT05898620
- Lead Sponsor
- Neurogene Inc.
- Brief Summary
This study will evaluate the safety profile of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.
- 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 given as a single administration 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 14
- 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 lack of 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
- 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
- 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 and exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Low Dose NGN-401 Dose Level 1 High Dose NGN-401 Dose Level 2
- Primary Outcome Measures
Name Time Method Incidence of Treatment Emergent Adverse Events (TEAEs) 5 years Incidence, type, severity, and frequency of TEAEs
Incidence of Serious Adverse Events (SAEs) 5 years Incidence, type, severity, and frequency of SAEs
Incidence of Adverse Events of Special Interest (AESIs) 5 years Incidence, type, severity, and frequency of AESIs
Incidence of clinical laboratory abnormalities 5 years Incidence, type, severity, and frequency of clinical laboratory abnormalities
Incidence of new physical and neurologic exam abnormalities 5 years Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (8)
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Montefiore Medical Center
🇺🇸New York, New York, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
The Children's Hospital at Westmead
🇦🇺Sydney, New South Wales, Australia
Royal Hospital for Children and Young People
🇬🇧Edinburgh, United Kingdom
Manchester University NHS Foundation Trust
🇬🇧Manchester, United Kingdom