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

Brief Title

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

Official Title

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

Brief 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.

Study Phase

Phase 1

Study Type


Primary Outcome

Incidence, severity, seriousness and relatedness to treatment of treatment emergent adverse events

Secondary Outcome

 Number of participants with abnormal vital signs


Tay-Sachs Disease


AXO-AAV-GM2 Starting Dose

Study Arms / Comparison Groups

Description:  AXO-AAV-GM2 infusion


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 15, 2021

Completion Date

June 2028

Primary Completion Date

November 2024

Eligibility Criteria

        Inclusion Criteria:

          1. 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

             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

             i. Diagnosis consistent with infantile-onset TSD or SD

             ii. 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. Current clinically significant infections including any requiring systemic treatment
             including but not limited to human immunodeficiency virus (HIV), Hepatitis A, B, or C

         11. 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

         12. Clinically significant laboratory abnormalities in liver functional tests, hematology,
             and blood chemistry parameters

         13. Subjects for whom any of the proposed study procedures or medications would be

         14. Failure to thrive, defined as falling 20 percentiles (20/100) in body weight in the 3
             months preceding Screening/Baseline

         15. Subject is not suitable for participation in the study in the opinion of the Principal




6 Months - 12 Years

Accepts Healthy Volunteers



Erika De Boever, DDS, PhD, 646-887-2651, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Sio Gene Therapies


 University of Massachusetts, Worcester

Study Sponsor

Erika De Boever, DDS, PhD, Study Director, Sio Gene Therapies

Verification Date

January 2021