Rett SyndromePhase 3NCT05898620
A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
A Phase 3 study testing NGN-401 in people with Rett Syndrome, run by Neurogene Inc. at 16 sites in 3 countries.
Trial summary
This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome. Read more about this study
- Who is it for?
- Ages 3 years and older, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- NGN-401
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 13 Jun 2023to Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
United States13 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Kennedy Krieger Institute
Baltimore, Maryland, 21205
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
UNC at Chapel Hill
Chapel Hill, North Carolina, 27514
Rush University Medical Center
Chicago, Illinois, 60612
Nationwide Children's Hospital
Columbus, Ohio, 43205
Texas Children's Hospital
Houston, Texas, 77030
Nicklaus Children's Hospital Research Institute
Miami, Florida, 33155
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Montefiore Medical Center
New York, New York, 10467
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
United Kingdom2 sites
Royal Hospital for Children and Young People
Edinburgh, EH16 4TJ
Manchester University NHS Foundation Trust
Manchester, M13 9WL
About this study
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)
This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.
Read the 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.
- Conditions
- Rett Syndrome
- Being tested
- NGN-401
- 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
- Medical subject headings
- Rett Syndrome, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Neurodevelopmental Disorders, Neurobehavioral Manifestations, Neurologic Manifestations, Intellectual Disability, Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGN-401Genetic
NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.
| Study group | Role | What they receive |
|---|---|---|
| Pediatric 1e15 vg dose (fully enrolled) | Experimental | Dose Level 1 for ages 4-10 years Receives: Genetic: NGN-401 |
| Adolescent/Adult 1e15 vg Dose (fully enrolled) | Experimental | Dose Level 1 for ages 11 years \& above Receives: Genetic: NGN-401 |
| Pediatric 3e15 vg dose (discontinued) | Experimental | Dose Level 2 for ages 4-10 years (discontinued) Receives: Genetic: NGN-401 |
| Pivotal Cohort | Experimental | Dose Level 1 for ages 3 and above Receives: Genetic: NGN-401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of NGN-401
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.
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start13 Jun 2023
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study treatment will be delivered via intracerebroventricular (ICV) injection. All study participants will receive the same intervention.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neurogene Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julie Jordan, MD, Study director, Neurogene Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05898620
- Sponsor's protocol ID
- RTT-200
- Status last verified
- Jun 2026
- First submitted
- 1 Jun 2023
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ross PD, Gadalla KKE, Thomson SR, Selfridge J, Bahey NG, Benito J, Burstein SR, McMinn R, Bolon B, Hector RD, Cobb SR. Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome. Sci Transl Med. 2025 Apr 2;17(792):eadq3614. doi: 10.1126/scitranslmed.adq3614. Epub 2025 Apr 2.
PubMed 40173263Jagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159/000539267. Epub 2024 May 9.
PubMed 38723617
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05898620
- Acronym / sponsor ID
- RTT-200
- Conditions
- Rett Syndrome
- Keywords
- Typical Rett Syndrome, MECP2, Rett Disorder, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Neurodevelopmental Disorders, Neurobehavioral Manifestations, Neurologic Manifestations
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Neurogene Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Jun 2023 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 12 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- The study treatment will be delivered via intracerebroventricular (ICV) injection. All study participants will receive the same intervention.
| Arm | Type | Receives |
|---|---|---|
| Pediatric 1e15 vg dose (fully enrolled) | Experimental | Genetic: NGN-401Dose Level 1 for ages 4-10 years |
| Adolescent/Adult 1e15 vg Dose (fully enrolled) | Experimental | Genetic: NGN-401Dose Level 1 for ages 11 years \& above |
| Pediatric 3e15 vg dose (discontinued) | Experimental | Genetic: NGN-401Dose Level 2 for ages 4-10 years (discontinued) |
| Pivotal Cohort | Experimental | Genetic: NGN-401Dose Level 1 for ages 3 and above |
Who may qualify
- Ages
- 3 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGN-401NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene. | Genetic | Adolescent/Adult 1e15 vg Dose (fully enrolled), Pediatric 1e15 vg dose (fully enrolled), Pediatric 3e15 vg dose (discontinued), Pivotal Cohort |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Derived from this study: PubMed 40173263Ross PD, Gadalla KKE, Thomson SR, Selfridge J, Bahey NG, Benito J, Burstein SR, McMinn R, Bolon B, Hector RD, Cobb SR. Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome. Sci Transl Med. 2025 Apr 2;17(792):eadq3614. doi: 10.1126/scitranslmed.adq3614. Epub 2025 Apr 2.
- Derived from this study: PubMed 38723617Jagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159/000539267. Epub 2024 May 9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Jordan, MD study director
Neurogene Inc.
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NGN-401 in people with Rett Syndrome, run by Neurogene Inc. at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, United Kingdom, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of NGN-401 (time frame: 52 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05898620, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.