Gene Therapy for Tay-Sachs and Sandhoff Diseases

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy, AXO-AAV-GM2, to treat Tay-Sachs and Sandhoff diseases, rare genetic disorders affecting the nervous system in children. The goal is to test the safety and effectiveness of the treatment by delivering healthy copies of the defective genes. Pediatric participants diagnosed with Tay-Sachs or Sandhoff who can perform certain basic physical or developmental tasks might be suitable candidates. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Do I need to stop taking my current medications for the trial?

If you are taking Zavesca® (miglustat) or Tanganil® (acetyl-leucine), you will need to stop these medications 30 days before the trial screening. For other medications, the trial protocol does not specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the AXO-AAV-GM2 gene therapy appears promising in early safety tests. In a study with two patients, the treatment was generally well-tolerated, and no major safety issues emerged. This gene therapy aims to help children with Tay-Sachs and Sandhoff diseases by providing healthy versions of the faulty genes. Although this trial remains in its early stages, initial results suggest that the treatment is manageable for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Tay-Sachs and Sandhoff diseases, which mainly focus on managing symptoms, AXO-AAV-GM2 is a gene therapy aiming to tackle the root cause of these conditions. This therapy uses a viral vector to deliver a healthy copy of the defective gene directly to the patient’s cells, potentially stopping disease progression. Researchers are excited about this treatment because it offers the possibility of a one-time administration that could significantly alter the disease course, which is a revolutionary approach compared to the continuous management required by existing therapies.

What evidence suggests that this trial's treatments could be effective for Tay-Sachs and Sandhoff diseases?

Research has shown that AXO-AAV-GM2 gene therapy could be a promising treatment for Tay-Sachs and Sandhoff diseases. In an earlier study, evidence from two patients indicated that the treatment was generally well-tolerated. This therapy adds working copies of the HEXA and HEXB genes, which help produce the HexA enzyme. This enzyme is crucial for breaking down certain fats in the brain. By restoring HexA function, the therapy aims to slow or stop the progression of these brain diseases. Although these early results are encouraging, further research is needed to fully understand the therapy's effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Terence Flotte, MD

Principal Investigator

University of Massachusetts Medical Health Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04669535

NCT04669535 | A Dose-escalation and Safety & Efficacy ... 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) ...

2. umassmed.edu umassmed.edu/news/news-archives/2021/02/first-patient-dosed-in-clinical-trial-of-gene-therapy-for-tay-sachs-and-sandhoff-disease/

First patient dosed in clinical trial of gene therapy for Tay- ... In 2019, clinical evidence from two patients under an investigator-initiated study found that treatment with AXO-AAV-GM2 was generally well ...

3. cats-foundation.org cats-foundation.org/wp-content/uploads/2022/01/AXO-AAV-GM2-Trial-Brochure-Jun2021.pdf

Gene Therapy Clinical Trial for Tay-Sachs and Sandhoff ... A Phase 1/2 clinical trial is being conducted to learn if an experimental gene therapy called AXO-. AAV-GM2 can help treat children with infantile and juvenile- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06614569

Study Details | NCT06614569 | Long-Term Follow-Up of ... This study is to continue Long-Term Follow-Up of Patients who were previously treated with AXO-AAV-GM2 Gene Therapy as treatment for Tay-Sachs or Sandhoff ...

5. ctv.veeva.com ctv.veeva.com/study/a-dose-escalation-and-safety-efficacy-study-of-axo-aav-gm2-in-tay-sachs-or-sandhoff-disease

A Dose-escalation and Safety & Efficacy Study of AXO-AAV ... 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 ...

6. checkrare.com checkrare.com/preliminary-results-from-gene-therapy-in-tay-sachs-disease-patients/

Preliminary Results from Gene Therapy in Tay-Sachs ... The first stage of this study provides early safety and proof-of-concept data in humans for the use of AAV gene therapy in patients with Tay-Sachs disease.