Brief Summary
This study will evaluate the efficacy and safety profiles 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 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.
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.
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:
* 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
Other inclusion and exclusion criteria apply.
* 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
Other inclusion and exclusion criteria apply.
Inclusion Criteria
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.
inclusion and
* 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.
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
Pathologic Processes
RTT
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
3 Years
NCT Id
NCT05898620
Org Class
Industry
Org Full Name
Neurogene Inc.
Org Study Id
RTT-200
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Baseline-Controlled, Open-Label, Multicenter, Single-Arm, Pivotal Study to Evaluate the Efficacy, Safety, and Tolerability of NGN-401 in Subjects With Rett Syndrome (Embolden)
Primary Outcomes
Outcome Description
Responders will be defined as participants who:
* Attain a CGI-I score of ≤ 3 ("minimally improved");
* and gain any one developmental milestone/skill from a list of 28, as captured through standardized video recordings and independently verified by blinded central raters.
* Attain a CGI-I score of ≤ 3 ("minimally improved");
* and gain any one developmental milestone/skill from a list of 28, as captured through standardized video recordings and independently verified by blinded central raters.
Outcome Measure
Efficacy of NGN-401
Outcome Time Frame
52 Weeks
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)
3
Investigators
Investigator Type
Principal Investigator
Investigator Name
Aleksandra Djukic
Investigator Email
adjukic@montefiore.org
Investigator Department
Neurology
Investigator Division
Child Neurology
Investigator Sponsor Organization
External
Study Department
Neurology
Study Division
Pediatric Neurology
Categories Mesh Debug
Child Development & Autism --- NEURODEVELOPMENTAL DISORDERS
Mental Health & Behavioral Research --- NEUROBEHAVIORAL MANIFESTATIONS
Brain, Spinal Cord & Nervous System --- NEUROLOGIC MANIFESTATIONS
Headaches & Migraine --- NEUROLOGIC MANIFESTATIONS
Substance Use and Addiction --- NEUROLOGIC MANIFESTATIONS
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
Child Development & Autism --- MENTAL DISORDERS
Mental Health & Behavioral Research --- MENTAL DISORDERS
Psychiatry & Behavioral Sciences --- MENTAL DISORDERS
Substance Use and Addiction --- MENTAL DISORDERS
MeSH Terms
RETT SYNDROME
GENETIC DISEASES, INBORN
GENETIC DISEASES, X-LINKED
NEURODEVELOPMENTAL DISORDERS
NEUROBEHAVIORAL MANIFESTATIONS
NEUROLOGIC MANIFESTATIONS
INTELLECTUAL DISABILITY
NERVOUS SYSTEM DISEASES
PATHOLOGIC PROCESSES
X-LINKED INTELLECTUAL DISABILITY
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM
MENTAL DISORDERS
SIGNS AND SYMPTOMS
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS