Rett Syndrome
Conditions
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
Brief summary
This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical 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.
Interventions
GENETICNGN-401
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.
Sponsors
Neurogene Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Central raters for the acquisition of a developmental milestone/skill from videos are blinded to the intervention and to the timing of the video.
Intervention model description
The study treatment will be delivered via intracerebroventricular (ICV) injection. All study participants will receive the same intervention.
Eligibility
Sex/Gender
FEMALE
Age
3 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of NGN-401 | 52 Weeks | 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. |
Countries
Australia, United Kingdom, United States
Contacts
STUDY_DIRECTORJulie Jordan, MD
Neurogene Inc.
Outcome results
None listed