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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Neurogene Inc.
- Enrollment
- 33
- Locations
- 30
- Primary Endpoint
- Efficacy of NGN-401
Study Overview
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.
Study Design
- Study Type
- Interventional
- 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.
Eligibility Criteria
- Ages
- 3 Years to — (Child, Adult, Older Adult)
- Sex
- Female
- Accepts 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 exclusion criteria apply.
Arms & Interventions
Pediatric 1e15 vg dose (fully enrolled)
Dose Level 1 for ages 4-10 years
Intervention: NGN-401 (Genetic)
Adolescent/Adult 1e15 vg Dose (fully enrolled)
Dose Level 1 for ages 11 years & above
Intervention: NGN-401 (Genetic)
Pivotal Cohort
Dose Level 1 for ages 3 and above
Intervention: NGN-401 (Genetic)
Pediatric 3e15 vg dose (discontinued)
Dose Level 2 for ages 4-10 years (discontinued)
Intervention: NGN-401 (Genetic)
Outcomes
Primary Outcomes
Efficacy of NGN-401
Time Frame: 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.
Secondary Outcomes
No secondary outcomes reported