A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
Purpose
This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.
Condition
- Rett Syndrome
Eligibility
- Eligible Ages
- Over 3 Years
- Eligible 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- The study treatment will be delivered via intracerebroventricular (ICV) injection. All study participants will receive the same intervention.
- 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.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Pediatric 1e15 vg dose (fully enrolled) |
Dose Level 1 for ages 4-10 years |
|
|
Experimental Adolescent/Adult 1e15 vg Dose (fully enrolled) |
Dose Level 1 for ages 11 years & above |
|
|
Experimental Pediatric 3e15 vg dose (discontinued) |
Dose Level 2 for ages 4-10 years (discontinued) |
|
|
Experimental Pivotal Cohort |
Dose Level 1 for ages 3 and above |
|
Recruiting Locations
Birmingham 4049979, Alabama 4829764 35233
More Details
- Status
- Recruiting
- Sponsor
- Neurogene Inc.
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.