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

Neurogene

Status and phase: Enrolling; Phase 3

Conditions: Rett Syndrome

Treatments: Genetic: NGN-401

Study type: Interventional

Funder types: Industry

Identifiers

NCT05898620

RTT-200

Details and patient eligibility

About

This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.

Full 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.

Enrollment: 33 estimated patients

Sex: Female

Ages: 3 to 10 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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33 participants in 4 patient groups

Pediatric 1e15 vg dose (fully enrolled)

Experimental group

Description:

Dose Level 1 for ages 4-10 years

Treatment:

Genetic: NGN-401

Adolescent/Adult 1e15 vg Dose (fully enrolled)

Experimental group

Description:

Dose Level 1 for ages 11 years \& above

Treatment:

Genetic: NGN-401

Pediatric 3e15 vg dose (discontinued)

Experimental group

Description:

Dose Level 2 for ages 4-10 years (discontinued)

Treatment:

Genetic: NGN-401

Pivotal Cohort

Experimental group

Description:

Dose Level 1 for ages 3 and above

Treatment:

Genetic: NGN-401