Brief Summary
This study will evaluate the safety profile of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.
Brief Title
A Novel, Regulated Gene Therapy (NGN-401) Study for Females With 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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+1 877-237-5020
Central Contact Email
medicalinfo@neurogene.com
Completion Date
Completion Date Type
Estimated
Conditions
Rett Syndrome
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 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
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
* 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.
* 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
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
* 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.
Inclusion 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 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
inclusion and
* 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
inclusion and
Gender
Female
Gender Based
false
Keywords
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
4 Years
NCT Id
NCT05898620
Org Class
Industry
Org Full Name
Neurogene Inc.
Org Study Id
RTT-200
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1/2, Open-Label Clinical Study to Evaluate Safety, Tolerability, and Efficacy of NGN-401 in Subjects With Rett Syndrome
Primary Outcomes
Outcome Description
Incidence, type, severity, and frequency of TEAEs
Outcome Measure
Incidence of Treatment Emergent Adverse Events (TEAEs)
Outcome Time Frame
5 years
Outcome Description
Incidence, type, severity, and frequency of SAEs
Outcome Measure
Incidence of Serious Adverse Events (SAEs)
Outcome Time Frame
5 years
Outcome Description
Incidence, type, severity, and frequency of AESIs
Outcome Measure
Incidence of Adverse Events of Special Interest (AESIs)
Outcome Time Frame
5 years
Outcome Description
Incidence, type, severity, and frequency of clinical laboratory abnormalities
Outcome Measure
Incidence of clinical laboratory abnormalities
Outcome Time Frame
5 years
Outcome Description
Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
Outcome Measure
Incidence of new physical and neurologic exam abnormalities
Outcome Time Frame
5 years
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
4
Investigators
Investigator Type
Principal Investigator
Investigator Name
Aleksandra Djukic
Investigator Email
adjukic@montefiore.org