Gene therapy for females with Rett syndrome
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)
This study is testing a new gene therapy to see if it can help girls with Rett syndrome by delivering a missing gene to their brains.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 33 (estimated) |
| Ages | 3 Years and up |
| Sex | Female |
| Sponsor | Neurogene Inc. Industry-sponsored |
| Locations | 16 sites (Birmingham, Alabama and 15 other locations) |
| Trial ID | NCT05898620 on ClinicalTrials.gov |
What this trial studies
This study evaluates the safety and efficacy of NGN-401, a novel gene therapy, in females diagnosed with typical Rett syndrome. It is a phase 1/2, open-label study that utilizes an adeno-associated viral vector serotype 9 (AAV9) to deliver a full-length human MECP2 gene, aiming to express therapeutic levels of the MECP2 protein. Participants will receive a single administration of the treatment under general anesthesia via intracerebroventricular delivery and will be monitored for safety and preliminary efficacy for five years, with an option for long-term follow-up for an additional ten years.
Who should consider this trial
Good fit: Ideal candidates are females diagnosed with typical Rett syndrome who have a documented mutation in the MECP2 gene.
Not a fit: Patients with normal or near-normal hand function or those with significant comorbid conditions may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could significantly improve the quality of life and functional outcomes for patients with Rett syndrome.
How similar studies have performed: While gene therapy approaches for genetic disorders are being explored, this specific application for Rett syndrome is novel and has not been extensively tested in prior studies.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Birmingham, Alabama and 15 other locations
- University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)
- UCSF Benioff Children's Hospital Oakland — Oakland, California, United States (Recruiting)
- Children's Hospital Colorado — Aurora, Colorado, United States (Recruiting)
- Nicklaus Children's Hospital Research Institute — Miami, Florida, United States (Recruiting)
- Rush University Medical Center — Chicago, Illinois, United States (Recruiting)
- Kennedy Krieger Institute — Baltimore, Maryland, United States (Recruiting)
- Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
- Montefiore Medical Center — New York, New York, United States (Recruiting)
- UNC at Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)
- Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)
- Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Not_yet_recruiting)
- Vanderbilt University Medical Center — Nashville, Tennessee, United States (Recruiting)
- Texas Children's Hospital — Houston, Texas, United States (Recruiting)
- The Children's Hospital at Westmead — Sydney, New South Wales, Australia (Active_not_recruiting)
- Royal Hospital for Children and Young People — Edinburgh, United Kingdom (Terminated)
- Manchester University NHS Foundation Trust — Manchester, United Kingdom (Terminated)
Study contacts
- Study coordinator: Contact Center
- Email: medicalinfo@neurogene.com
- Phone: +1 877-237-5020
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.