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A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease | Clinical Trials | Clareo Health

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A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease

A Two-Stage, Dose-Escalation and Safety & Efficacy Study of Bilateral Intraparenchymal Thalamic and Intracisternal/Intrathecal Administration of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease

NCT04669535•Terence Flotte

View on ClinicalTrials.gov

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.

Eligibility

Age

0 - 12 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Male or female participants with genetically diagnosed TSD or SD mutations of either HEXA gene or HEXB gene
•a. Stage 1 juvenile-onset participants must be ≥ 2 years old and ≤ 12 years old at time of gene transfer i. Diagnosis consistent with juvenile-onset TSD or SD b. Stage 1 infantile-onset participants must be between 6-20 months of age at the time of gene transfer i. Diagnosis consistent with infantile-onset TSD or SD
•2. 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:
•1. 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.
•2. Fine Motor Function
•* For Participants aged 4-12 years: A Manual Ability Classification System (MACS) score of I, II, III, or IV. The minimum level of manual ability (level IV) corresponds to 'Handles a limited selection of easily managed objects in adapted situations'.
•* For participants aged 2-4 years: attainment of fine motor function/coordination abilities and milestones with normal or a reduced quality of performance. That is, the ability to coordinate fingers and both hands to play, such as swinging a bat or opening a container (pathways.org) OR the ability to use fingertips to pick up small objects, i.e., the child uses pad of his/her thumb and any fingertip to grasp a pellet or small object as described in BSID III Fine Motor Sub-test Item #26. .
•3. Speech:
•* For participants aged 4-12 years, a speech disturbance score of 0, 1, 2 or 3 on the speech disturbance subset of the Scale for Assessment and Rating of Ataxia (SARA). The minimum speech requirement is a speech disturbance in which most words can be understood, with occasional words difficult to understand secondary to dysarthria.
•* Participants aged 2-4 years who have attained the communication milestone of ability to consistently use 2-3 word phrases may be assessed in line with this criterion using the speech disturbance subset of the SARA.
+20 more criteria

Exclusion Criteria

•1. Presence of G269S or W474C mutation in HEXA
•2. 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.
•3. History of multiple aspiration pneumonias occurring in the past twelve months.
•4. Respiratory support in the form of ventilation (invasive or non-invasive).
•5. History of drug-resistant seizures or status epilepticus
•6. History and/or findings of spinal cord disease that would preclude the lumbar puncture and ICM/IT infusion procedures including:
•* Infectious process involving the spinal canal which may cause adhesions or septations in the spinal and/or subarachnoid space
•* Previous spinal surgeries
•* History of trauma, bleeding in the spinal canal
•* Vascular or cystic lesions, or any other mass lesion
+23 more criteria

Locations (2)

Massachusetts General Hospital, Center for Rare Neurological Diseases

Boston, Massachusetts, United States

University of Massachusetts Medical Health Center

Worcester, Massachusetts, United States

Key Dates

Start Date

January 15, 2021

Primary Completion Date

May 23, 2024

Completion Date

December 16, 2024

Last Updated

September 2, 2025

Enrollment

ACTUAL participants

Conditions

Tay-Sachs DiseaseSandhoff Disease

Interventions

AXO-AAV-GM2 Starting Dose

BIOLOGICAL

AXO-AAV-GM2 Low Dose

BIOLOGICAL

AXO-AAV-GM2 Middle Dose

BIOLOGICAL

AXO-AAV-GM2 High Dose

BIOLOGICAL

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

NCT02254863

AdrenoleukodystrophyBatten Disease+10 more

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ACTIVE_NOT_RECRUITING

Long-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease

NCT06614569

GM2 GangliosidosisTay Sachs Disease+1 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 2, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease

Inclusion Criteria

Exclusion Criteria

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

Long-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease

Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

Synergistic Enteral Regimen for Treatment of the Gangliosidoses

A Phase I Study of Pyrimethamine in Patients With GM2 Gangliosidosis

Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)