A Novel, Regulated Gene Therapy (NGN-401) Study for Female Children With Rett Syndrome

• ClinicalTrials.gov Identifier: NCT05898620
• Recruitment Status: Recruiting
• First Posted: June 12, 2023
• Last Update Posted: March 13, 2024
• Sponsor: Neurogene Inc.
• Information provided by (Responsible Party): Neurogene Inc.

Tracking Information

• First Submitted Date: June 1, 2023
• First Posted Date: June 12, 2023
• Last Update Posted Date: March 13, 2024
• Actual Study Start Date: June 13, 2023
• Estimated Primary Completion Date: October 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2023)

• Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 5 years ]
  Incidence, type, severity, and frequency of TEAEs
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: 5 years ]
  Incidence, type, severity, and frequency of SAEs
• Incidence of Adverse Events of Special Interest (AESIs) [ Time Frame: 5 years ]
  Incidence, type, severity, and frequency of AESIs
• Incidence of clinical laboratory abnormalities [ Time Frame: 5 years ]
  Incidence, type, severity, and frequency of clinical laboratory abnormalities
• Incidence of new physical and neurologic exam abnormalities [ Time Frame: 5 years ]
  Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities

Original Primary Outcome Measures (submitted: June 1, 2023)

• Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 5 years (multiple visits) ]
  Incidence, type, severity, and frequency of TEAEs
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: 5 years (multiple visits) ]
  Incidence, type, severity, and frequency of SAEs
• Incidence of Adverse Events of Special Interest (AESIs) [ Time Frame: 5 years (multiple visits) ]
  Incidence, type, severity, and frequency of AESIs
• Incidence of clinical laboratory abnormalities [ Time Frame: 5 years (multiple visits) ]
  Incidence, type, severity, and frequency of clinical laboratory abnormalities
• Incidence of new physical and neurologic exam abnormalities [ Time Frame: 5 years (multiple visits) ]
  Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Novel, Regulated Gene Therapy (NGN-401) Study for Female Children With Rett Syndrome
• Official Title: A Phase 1/2, Open-Label Clinical Study to Evaluate Safety, Tolerability, and Efficacy of NGN-401 in Pediatric Subjects With Rett Syndrome
• Brief Summary: This study will evaluate the safety profile of the investigational gene therapy, NGN-401, in female children with typical Rett syndrome.

Detailed Description

The study is a phase 1/2, open-label study designed to assess the safety, tolerability, and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9), using Neurogene's proprietary transgene regulation technology. NGN-401 contains a full-length human MECP2 gene which is designed to express therapeutic levels of the MECP2 protein while avoiding overexpression.

The study treatment will be administered under general anesthesia via intracerebroventricular (ICV) delivery. Each participant will be followed for safety and preliminary efficacy for 5 years after treatment and is expected to enroll in a long-term follow-up study for 10 years.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rett Syndrome

Intervention

Genetic: NGN-401

NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.

Study Arms

• Experimental: Low Dose
  Dose Level 1
  Intervention: Genetic: NGN-401
• Experimental: High Dose
  Dose Level 2
  Intervention: Genetic: NGN-401

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 11, 2024): 16
• Original Estimated Enrollment (submitted: June 1, 2023): 5
• Estimated Study Completion Date: October 2029
• Estimated Primary Completion Date: October 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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 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 needed for study related procedures
• Grossly abnormal psychomotor development in the first 6 months of life
• A history of other genetic disorders or neurological conditions, such as stroke, brain tumor, or autoimmune processes affecting the central nervous system

Other inclusion or exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 4 Years to 10 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Contact Center; +1 877-237-5020; medicalinfo@neurogene.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05898620
• Other Study ID Numbers: RTT-200
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Neurogene Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Neurogene Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Julie Jordan, MD; Neurogene Inc.

• PRS Account: Neurogene Inc.
• Verification Date: March 2024