What is AAV9-GLB1 studying for GM1 gangliosidosis?

AAV9-GLB1 is a gene therapy being studied to see if it can help improve symptoms in children with Type I and Type II GM1 gangliosidosis, a serious nerve cell disorder. Researchers want to understand the safety and effects of this therapy. The study is supported by the National Human Genome Research Institute (NHGRI). Participants will be closely monitored throughout the trial.

Who may be eligible for this GM1 gangliosidosis clinical trial?

Children aged between 6 months and 12 years with a confirmed diagnosis of Type I or Type II GM1 gangliosidosis may be eligible. Both males and females can participate. Participants must have enzyme deficiency confirmed by lab tests and meet other health criteria. Please review eligibility criteria for more details.

Is there any cost to participate in this GM1 gangliosidosis clinical trial?

Study-related care, including the gene therapy and all trial visits, is provided at no cost. However, personal travel or accommodation expenses are not guaranteed to be covered and may vary. Participants and families should plan accordingly for any additional costs.

Actively Recruiting

Phase 1

Phase 2

Age: 6Months - 12Years

All Genders

ID03952637

Phase 12 Study of Intravenous AAV9 Gene Therapy Delivering Beta-galactosidase for Treating Type I and Type II GM1 Gangliosidosis in Children

Led by National Human Genome Research Institute (NHGRI) · Updated on 2025-12-11

Participants Needed

Research Sites

N/A

Total Duration

AI-Summary

What this Trial Is About

Researchers are evaluating a gene therapy called AAV9-GLB1 for treating Type I and Type II GM1 gangliosidosis, a rare and fatal disorder that destroys nerve cells due to a deficiency in the enzyme beta-galactosidase. This trial aims to test if the gene therapy can help improve symptoms related to these types of GM1 gangliosidosis. The study is a Phase 12 non-randomized trial focusing on safety and effectiveness in children ranging from 6 months to 12 years old, sponsored by the National Human Genome Research Institute NHGRI. Participants will receive a single intravenous infusion of the AAV9-GLB1 gene therapy at doses determined in stages. In Stage 1, different groups of Type I and Type II subjects will receive varying doses to assess safety. Immune system modulation drugs such as rituximab, sirolimus, methylprednisolone, and prednisone will be given before and after gene therapy to reduce immune reactions. Participants will stay at the study site for 8 to 10 weeks initially and may remain for additional safety monitoring after infusion. Stage 2 will administer the dose selected based on Stage 1 data, with further assessments planned. During the study, participants will undergo many tests including blood and urine tests, heart and hearing assessments, ultrasounds, EEGs, lumbar punctures, MRIs, bone scans, IQ and speech tests, and neurological exams. Central line placement and skin biopsies may also be done. Follow-up visits will occur at 3 and 6 months after treatment, then every 6 months for 2 years, and again at 3 years, with yearly visits for 2 more years in an extension study. Researchers will monitor safety, brain development, neurological function, motor skills, and immune responses throughout the study period.

CONDITIONS

Brief Title

A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis

Who Can Participate

Age: 6Months - 12Years

All Genders

Eligibility Criteria

You may qualify if you...

Male or female subjects 6 months to 12 months old with Type I GM1 gangliosidosis at time of consent
Male or female subjects older than 6 months and younger than 12 years with Type II GM1 gangliosidosis at time of consent
Biallelic mutations in the GLB1 gene confirmed
Documented deficiency of Beta-galactosidase enzyme by clinical lab testing
Phenotype consistent with Type I or Type II GM1 gangliosidosis
For Type I symptomatic subjects: symptom onset at or before 6 months with rapid progression including developmental delay and hypotonia
For Type I pre-symptomatic subjects: mutations confirmed to be associated with Type I
For Type II subjects: Vineland-3 Adaptive Behavior composite score of at least 40
AAV9 antibody titers less than or equal to 1:50
Agree to live within 50 miles of study site for at least 1 month after treatment

You will not qualify if you...

AAV9 antibody titers greater than 1:50
Contraindications to medications used in the study
Serious illness preventing travel to the study site
Unwillingness to undergo required study procedures
Use of other unapproved or experimental therapies for GM1 gangliosidosis in the past 60 days
Prior gene therapy or stem cell transplantation
Pregnancy or breastfeeding
Immunizations within one month before screening
Evidence of cardiomyopathy or other unsafe cardiac disease
Presence of ferromagnetic devices preventing MRI imaging
Medical conditions interfering with study conduct or assessments
History of HIV, hepatitis A, B, or C, or tuberculosis
Chemotherapy, radiotherapy, or immunosuppressive therapy within past 30 days (corticosteroids may be allowed)
Clinically significant abnormal lab values
Failure to thrive with significant recent weight loss
Underlying immune function defects
History of multiple severe infections

Research Team

Jean M Johnston

Cynthia J Tifft, M.D.

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