The AXO-GM2-001 study is an open-label, two-stage clinical trial designed to evaluate safety and dose-escalation (Stage 1) and safety and efficacy (Stage 2) of a bilateral thalamic and intracisternal/intrathecal infusion of AXO-AAV-GM2 in pediatric participants with GM2 Gangliosidosis (also known as Tay-Sachs or Sandhoff Diseases), a set of rare and fatal pediatric neurodegenerative genetic disorders caused by defects in the HEXA (leading to Tay-Sachs disease) or HEXB (leading to Sandhoff disease) genes that encode the two subunits of the β-hexosaminidase A (HexA) enzyme. AXO-AAV-GM2 is an investigational gene therapy that aims to restore HexA function by introducing a functional copy of the HEXA and HEXB genes via co-administration of two vectors utilizing the neurotropic adeno-associated virus recombinant human 8 serotype (AAVrh.8) capsid carrying the human HEXA or HEXB cDNA. The trial is expected to enroll pediatric participants with Tay-Sachs or Sandhoff Diseases, where infantile-onset participants will range from 6 months to 20 months old, and juvenile-onset participants will range from 2 years to 12 years old.

NCT04669535

Conditions

1. Tay-Sachs Disease
2. Sandhoff Disease

Interventions

1. Biological: AXO-AAV-GM2 Starting Dose
2. Biological: AXO-AAV-GM2 Low Dose
3. Biological: AXO-AAV-GM2 Middle Dose
4. Biological: AXO-AAV-GM2 High Dose

MeSH:Tay-Sachs Disease Sandhoff Disease

Current or historical ability to sit without support for at least 5 seconds 2. Surgical readiness for gene transfer by the routes of administration confirmed by the study neurosurgeon, based on examination and magnetic resonance imaging (MRI) findings 3. Subjects receiving off-label Zavesca® (miglustat) and/or Tanganil® (acetyl-leucine) must be willing to discontinue these therapies 30 days prior to the start of screening 4. Ability to reliably travel to the study sites for study visits according to the Schedule of Assessments 5. Subjects must have a swallowing evaluation test performed (within 6 months) prior to administration of gene replacement therapy Exclusion Criteria: 1. Presence of G269S or W574C mutation 2. History of drug-resistant seizures or status epilepticus 3. History and/or findings of spinal cord disease that would preclude the lumbar puncture and ICM/IT infusion procedures 4. The subject's parent(s) or legal guardian(s) is unable to understand the nature, scope, and possible consequences of the study, or does not agree to comply with the protocol defined schedule of assessments 5. Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered 6. Immunizations of any kind in the month prior to screening 7. Cardiomyopathy or other cardiac disease based on echocardiogram and/or electrocardiogram, (ECG) that in the opinion of the Investigator would deem the subject unsafe to undergo surgical gene transfer 8. Indwelling ferromagnetic devices that would preclude MRI//MRS/DTI imaging 9. Ongoing medical condition that is deemed by the Investigator to interfere with the conduct or assessments of the study 10. --- G269S ---