Neuronal Ceroid Lipofuscinosis CLN5
Conditions
Keywords
Batten Disease, Neuronal Ceroid Lipofuscinosis Disease, Neuronal Ceroid Lipofuscinosis Subtype 5 Disease, NCL, Gene Therapy, Gene Transfer, CLN5, CLN
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.
Interventions
GENETICNGN-101
Participants with confirmed mutations in the CLN5 gene who meet all the inclusion and none of the exclusion criteria will be treated with a single intracerebroventricular (ICV) dose and a single intravitreal (IVT) dose of the study treatment.
Sponsors
Neurogene Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation cohort study of NGN-101 administered by intracerebroventricular (ICV) infusion and intravitreal (IVT) injection; cohorts will be assigned sequentially.
Eligibility
Sex/Gender
ALL
Age
3 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
* Age from 3 to 9 years (Child) * Molecular genetic diagnosis of the CLN5 gene * Confirmed clinical diagnosis of CLN5 disease * Impaired motor and/or language function and/or impaired visual acuity * Written informed consent from parent or legal guardian and assent from study participant, if appropriate * Able to comply with protocol required assessments (laboratory sample collection, lumbar puncture (LP), nerve conduction studies (NCS), magnetic resonance imaging (MRI), etc.), which may require sedation or general anesthesia * Able to walk with or without assistance (assistance may include a walker, braces, or with one hand held) * Agree to reside within a 1-hour drive of the study site for at least 6 months following treatment (or a safely drivable distance for the study participant and caregivers according to investigator's discretion)
Exclusion criteria
* Has another neurologic disease or illness that may have caused cognitive decline before study entry * Known pathogenic or clinically suspected variant in a seizure associated genetic mutation besides CLN5 * Any active infections or severe infections within the 30 days prior to study treatment administration * Presence of a concomitant medical condition that precludes intracerebroventricular (ICV) injection, lumbar puncture (LP), or use of anesthetics needed for study-related procedures * Presence of any concomitant medical conditions that preclude intravitreal (IVT) administration * Has status epilepticus that lasts longer than 5 minutes or having more than 1 seizure within a 5-minute period, without returning to a normal level of consciousness between episodes within 12 weeks before study treatment * Total anti-AAV9 antibody titer greater than 1:400 * Any anticipated need for major surgery in the next 24 months * Participation in an Investigational New Drug, Investigational Device Exemption, or equivalent clinical study in the past 6 months * Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered * Participation in other investigational studies and non-interventional studies that have similar study assessments as this protocol while the study participant is enrolled in this study with the exception of sister studies sponsored by Neurogene * History of or current chemotherapy, radiotherapy, or other immunosuppressive therapy within the past 3 months * Use of prohibited medications * Immunizations of any kind in the 45 days prior to study treatment * Requiring daytime or nighttime ventilatory support at the time of Screening * Any item which would exclude the study participant from being able to undergo brain magnetic resonance imaging (MRI) according to local institutional policy * Known allergies or hypersensitivities to the required immunosuppression regime
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events (TEAEs) | 5 years (multiple visits) | Incidence, type, severity, and frequency of TEAEs |
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 color vision | 5 years (multiple visits) | Change from baseline in color vision measured using Ishihara color blindness testing |
| 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 Caregiver global impression of change | 5 years (multiple visits) | Caregiver global impression of change throughout the study |
| 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) |
Countries
United Kingdom, United States
Outcome results
None listed