A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease (NCT04669535) | Clinical Trial Compass
TerminatedPhase 1
A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease
Stopped: Sponsor withdrew from the study and there was a lack of funding to complete stage 2 of the designed study.
United States9 participantsStarted 2021-01-15
Plain-language summary
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.
Who can participate
Age range
6 Months – 12 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Male or female participants with genetically diagnosed TSD or SD mutations of either HEXA gene or HEXB gene
. Juvenile onset participants must demonstrate a minimum of 2 of the following age-appropriate clinical features/abilities, confirmed by the site examiner at the time of screening and reaffirmed prior to the initiation of immunosuppression:
. A Gross Motor Function Classification-MLD (GMFC-MLD) score of 0, 1 or 2. The minimum gross motor function (GMFC-MLD level 2) is the 'ability to walk with support and walking without support is not possible (fewer than 5 steps)'. (Participants aged 2-12 years) Note: Any form of support is permitted; however, the participant must initiate each step and complete it for a total of 5 steps.
. Fine Motor Function
. Speech:
. Infantile onset participants must demonstrate current\* or historical† ability to sit without support for at least 5 seconds
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Incidence, Severity, Seriousness and Relatedness to Treatment of Treatment Emergent Adverse Events
Timeframe: At least through 24 weeks post-treatment (infantile-onset participants) to 48 weeks post-treatment (juvenile-onset participants). All AEs are reported through the transition of the study to long-term follow-up.
. Head control - While supine, with head in midline turns head symmetrically (score of 3 on GMFM item 1)
. Uses hands to support self while sitting
Exclusion criteria
. Presence of G269S or W474C mutation in HEXA
. Evidence of lower respiratory tract aspiration not easily manageable with thickening of feedings or substitution of a modified bottle nipple, as judged on a multi-texture contrast swallow.
. History of multiple aspiration pneumonias occurring in the past twelve months.
. Respiratory support in the form of ventilation (invasive or non-invasive).
. 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 including:
. The participant'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