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

Rett Syndrome Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05898620
• Other study ID #: RTT-200
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 13, 2023
• Est. completion date: October 2029

Study information

• Verified date: March 2024
• Source: Neurogene Inc.
• Contact: Contact Center
• Phone: +1 877-237-5020
• Email: medicalinfo[@]neurogene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety profile of the investigational gene therapy, NGN-401, in female children with typical Rett syndrome.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: October 2029
• Est. primary completion date: October 2029
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 4 Years to 10 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Texas Children's Hospital	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Neurogene Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events (TEAEs)	Incidence, type, severity, and frequency of TEAEs	5 years
Primary	Incidence of Serious Adverse Events (SAEs)	Incidence, type, severity, and frequency of SAEs	5 years
Primary	Incidence of Adverse Events of Special Interest (AESIs)	Incidence, type, severity, and frequency of AESIs	5 years
Primary	Incidence of clinical laboratory abnormalities	Incidence, type, severity, and frequency of clinical laboratory abnormalities	5 years
Primary	Incidence of new physical and neurologic exam abnormalities	Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities	5 years