Clinical trial NCT05898620: A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
Official title: A Phase 1/2, Open-Label Clinical Study to Evaluate Safety, Tolerability, and Efficacy of NGN-401 in Subjects With Rett Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Rett Syndrome
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
Heredodegenerative Disorders, Nervous System
Pathologic Processes
RTT
Lead sponsor: Neurogene Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-12
Enrollment: 14
Sex: FEMALE
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety profile of the investigational gene therapy, NGN-401, in females 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 given as a single administration 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.

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 lack of 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
* 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 and exclusion criteria apply.

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 5 years
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: 5 years
measure: Incidence of Adverse Events of Special Interest (AESIs)
timeFrame: 5 years
measure: Incidence of clinical laboratory abnormalities
timeFrame: 5 years
measure: Incidence of new physical and neurologic exam abnormalities
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Sydney
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Children and Young People
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
affiliation: Neurogene Inc.
name: Julie Jordan, MD
role: STUDY_DIRECTOR
References: