A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease
Tay-Sachs Disease, Sandhoff Disease
About this trial
This is an interventional treatment trial for Tay-Sachs Disease focused on measuring GM2 Gangliosidosis, Hexosaminidase A Deficiency, HexA Deficiency, TSD, SD, Lysosomal Storage Disorders, Tay-Sachs Disease, Sandhoff Disease
Eligibility Criteria
Inclusion Criteria:
Male or female subjects born between 37 - 42 weeks gestation with genetically diagnosed TSD or SD mutations of either HEXA gene or HEXB gene
a. Juvenile-onset subjects must be ≥ 2 years old and ≤ 12 years old at time of gene transfer
i. Diagnosis consistent with juvenile-onset TSD or SD
b. Infantile-onset subjects must be between 6-20 months of age at the time of gene transfer
i. Diagnosis consistent with infantile-onset TSD or SD
ii. Current or historical ability to sit without support for at least 5 seconds
- Surgical readiness for gene transfer by the routes of administration confirmed by the study neurosurgeon, based on examination and magnetic resonance imaging (MRI) findings
- 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
- Ability to reliably travel to the study sites for study visits according to the Schedule of Assessments
- Subjects must have a swallowing evaluation test performed (within 6 months) prior to administration of gene replacement therapy
Exclusion Criteria:
- Presence of G269S or W574C mutation
- History of drug-resistant seizures or status epilepticus
- History and/or findings of spinal cord disease that would preclude the lumbar puncture and ICM/IT infusion procedures
- 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
- Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
- Immunizations of any kind in the month prior to screening
- 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
- Indwelling ferromagnetic devices that would preclude MRI//MRS/DTI imaging
- Ongoing medical condition that is deemed by the Investigator to interfere with the conduct or assessments of the study
- Current clinically significant infections including any requiring systemic treatment including but not limited to human immunodeficiency virus (HIV), Hepatitis A, B, or C
- History of or current chemotherapy, radiotherapy or other immunosuppressive therapy within the past 30 days. Corticosteroid treatment may be permitted at the discretion of the PI
- Clinically significant laboratory abnormalities in liver functional tests, hematology, and blood chemistry parameters
- Subjects for whom any of the proposed study procedures or medications would be contraindicated
- Failure to thrive, defined as falling 20 percentiles (20/100) in body weight in the 3 months preceding Screening/Baseline
- Subject is not suitable for participation in the study in the opinion of the Principal Investigator
Sites / Locations
- Massachusetts General Hospital, Center for Rare Neurological DiseasesRecruiting
- University of Massachusetts Medical Health CenterRecruiting
Arms of the Study
Arm 1
Experimental
AXO-AAV-GM2
AXO-AAV-GM2 infusion