Gene Therapy Study for Children With CLN5 Batten Disease
- Conditions
- Neuronal Ceroid Lipofuscinosis CLN5
- Interventions
- Genetic: NGN-101
- Registration Number
- NCT05228145
- Lead Sponsor
- Neurogene Inc.
- Brief Summary
This is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with Neuronal Ceroid Lipofuscinosis (Batten) Subtype 5 (CLN5) disease.
- Detailed Description
The study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding human ceroid-lipofuscinosis neuronal protein 5 (CLN5) in subjects with CLN5 Batten disease. The study treatment will be delivered via intracerebroventricular (ICV) and intravitreal (IVT) injection on the same day. Each participant will be followed for safety and efficacy for 5 years after treatment. Efficacy assessments in this study will evaluate motor, language, visual and cognitive function.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 NGN-101 The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt). Cohort 2 NGN-101 The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt). Cohort 3 NGN-101 The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt).
- Primary Outcome Measures
Name Time Method Incidence of Serious Adverse Events (SAEs) 5 years (multiple visits) Incidence, type, severity, and frequency of SAEs
Incidence of clinical laboratory abnormalities 5 years (multiple visits) Incidence, type, severity, and frequency of clinical laboratory abnormalities
Incidence of Treatment Emergent Adverse Events (TEAEs) 5 years (multiple visits) Incidence, type, severity, and frequency of TEAEs
Incidence of new nerve conduction study (NCS) abnormalities 5 years (multiple visits) Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities
Incidence of new physical and neurologic exam abnormalities 5 years (multiple visits) Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
- Secondary Outcome Measures
Name Time Method Change in Spectral Domain-Optical Coherence Tomography (SD-OCT) 5 years (multiple visits) Change from baseline in SD-OCT parameters including Ellipsoid Zone (EZ) defect area measurements, macular volume and thickness, retinal nerve fiber layer thickness, and ganglion cell layer thickness
Change in Unified Batten Diseases Rating Scale (UBDRS) 5 years (multiple visits) Change from baseline in total score and individual domains of the Unified Batten Diseases Rating Scale (UBDRS; total score 0 to 277, with higher scores indicating worse function)
Change in color vision 5 years (multiple visits) Change from baseline in color vision measured using Ishihara color blindness testing
Change in Hamburg Scale, Motor and Language domain scores 5 years (multiple visits) Change from baseline in Hamburg Scale, Motor and Language domain scores (each domain is rated from 0 to 3, with 3 reflecting normal function for age and 0 reflecting complete loss of function)
Change in visual acuity measurements 5 years (multiple visits) Change from baseline in visual acuity measured using Teller acuity cards, Lea symbol chart, Landolt C chart, or low contrast visual acuity (measure to be used will depend on subject's level of cognitive and visual function)
Change in Caregiver global impression of change 5 years (multiple visits) Caregiver global impression of change throughout the study
Trial Locations
- Locations (2)
University of Rochester
🇺🇸Rochester, New York, United States
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom