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

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.

Conditions

• Tay-Sachs Disease
• Sandhoff Disease

Interventions

BIOLOGICAL

AXO-AAV-GM2 Starting Dose

1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).

BIOLOGICAL

AXO-AAV-GM2 Low Dose

1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).

BIOLOGICAL

AXO-AAV-GM2 Middle Dose

1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).

BIOLOGICAL

AXO-AAV-GM2 High Dose

1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).

Sponsors & Collaborators

• University of Massachusetts, Worcester

  collaborator OTHER

• Massachusetts General Hospital

  collaborator OTHER

• Terence Flotte

  lead OTHER

Principal Investigators

• Terence Flotte, MD · University of Massachusetts Medical Health Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

6 Months

Max Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-01-15

Primary Completion

2024-05-23

Completion

2024-12-16

FDA Drug

Yes

Countries

• United States

Study Locations