Gene Therapy for Tay-Sachs and Sandhoff Diseases

Recruiting at 1 trial location

Overseen By Terence Flotte

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Terence Flotte

Must not be taking: Zavesca, Tanganil

Disqualifiers: G269S/W474C mutation, Respiratory support, Drug-resistant seizures, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

9 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Terence Flotte, MD

Principal Investigator

University of Massachusetts Medical Health Center

Eligibility Criteria

This trial is for pediatric patients with Tay-Sachs or Sandhoff Diseases. Infants must be 6-20 months old and able to sit without support, while juveniles should be 2-12 years old with certain clinical features. Participants can't have had previous gene therapy, need to stop specific treatments before joining, and must travel reliably to the study site.

Inclusion Criteria

I am cleared for gene therapy by a neurosurgeon after an exam and MRI.

I was born full-term and have a genetic diagnosis of TSD or SD.

My child is between 6-20 months old and has been diagnosed with infantile-onset TSD or SD.

Exclusion Criteria

You have a heart condition that makes it unsafe for you to have gene transfer surgery, as determined by the doctor.

I am not allergic or unable to take sirolimus or trimethoprim/sulfamethoxazole.

I do not have any serious infections, including HIV or Hepatitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation (Stage 1)

Evaluation of safety and dose-escalation of AXO-AAV-GM2 infusion

8 weeks

Safety and Efficacy (Stage 2)

Evaluation of safety and efficacy of AXO-AAV-GM2 infusion

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• AXO-AAV-GM2 High Dose
• AXO-AAV-GM2 Low Dose
• AXO-AAV-GM2 Middle Dose
• AXO-AAV-GM2 Starting Dose

Trial Overview The AXO-GM2-001 study tests different doses of AXO-AAV-GM2 gene therapy delivered into the brain and spinal fluid of children with genetic disorders affecting nerve cells. It aims to restore enzyme function by introducing healthy genes using a virus vector in two stages: dose escalation then safety and efficacy.

Participant Groups

Group I: AXO-AAV-GM2 Experimental Treatment 4 Interventions

AXO-AAV-GM2 infusion

Who Is Running the Clinical Trial?

Terence Flotte

Lead Sponsor

Trials

2

Recruited

20+

Sio Gene Therapies

Lead Sponsor

Trials

4

Recruited

100,000+

University of Massachusetts, Worcester

Collaborator

Trials

372

Recruited

998,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+