Actively Recruiting
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
Led by National Human Genome Research Institute (NHGRI) · Updated on 2025-12-11
54
Participants Needed
1
Research Sites
436 weeks
Total Duration
On this page
Sponsors
N
National Human Genome Research Institute (NHGRI)
Lead Sponsor
S
Sio Gene Therapies
Collaborating Sponsor
AI-Summary
What this Trial Is About
Background: GM1 gangliosidosis is a disorder that destroys nerve cells. It is fatal. There is no treatment. People with GM1 are deficient in a certain enzyme. A gene therapy may help the body make this enzyme. This could improve GM1 symptoms. Objective: To test if a gene therapy helps Type I and Type II GM1 gangliosidosis symptoms. Eligibility: Type I subjects will be male and female \>= 6 months \<= 12 months of age at the time of full ICF signing. Type II subjects will be male and female \> 12 months old and \< 12 years old at the time of full ICF signing. Design: Participants will be screened with their medical history and a phone survey. Participants will stay at NIH for 8-10 weeks. Participants will have baseline tests: Blood, urine, and heart tests Hearing tests Ultrasound of abdomen EEG: Sticky patches on the participant s head will measure brain function. Lumbar puncture: A needle will be stuck into the participant s spine to remove fluid. MRI scans, bone x-rays, and bone scans: Participants will lie in a machine that takes pictures of the body IQ tests Neurology exams Central line placement Skin biopsy: A small piece of the participant s skin will be removed. Speech tests Participants will have an x-ray while swallowing food. Participants will take drugs by mouth and IV. This will get their immune system ready for therapy. Participants will get the gene therapy by IV. They may stay at NIH for a week to watch for side effects. Participants will have visits 3 and 6 months after treatment. Then visits will be every 6 months for 2 years. Then they will have a visit at 3 years. Visits will take 4-5 days. Participants will return to NIH once a year for 2 years for tests in an extension study....
CONDITIONS
Official 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
Eligibility Criteria
You may qualify if you...
- Type I subjects must be male or female aged 6 to 12 months at full consent signing
- Type II subjects must be male or female older than 6 months and younger than 12 years at full consent signing
- Must have biallelic mutations in GLB1
- Documented deficiency of beta-galactosidase enzyme confirmed by clinical laboratory testing
- Phenotype consistent with diagnosis of Type I or Type II GM1 gangliosidosis
- Type I symptomatic subjects must have symptom onset at or before 6 months of age with rapid progression, developmental delay, and hypotonia
- Type I pre-symptomatic subjects must have mutations associated with Type I subtype
- Type II subjects must have symptom onset after the first year of life
- Vineland-3 Adaptive Behavior composite standard score of 40 or higher for Type II subjects
- AAV9 antibody titers must be 1:50 or lower
- Must agree to live within 50 miles of the study site for at least 1 month after treatment
You will not qualify if you...
- AAV9 antibody titers greater than 1:50
- Contraindications to required medications
- Serious illness preventing travel to the study site
- Unwillingness to undergo study interventions
- Use of unapproved, off-label, or experimental therapies for GM1 gangliosidosis within the last 60 days
- Previous participation in gene therapy or stem cell transplant studies
- Pregnant or breastfeeding
- Immunizations within 1 month before screening
- Evidence of cardiomyopathy or other cardiac disease deemed unsafe for participation
- Presence of ferromagnetic devices preventing MRI procedures
- Medical conditions interfering with study conduct or assessments
- History of HIV, hepatitis A, B, or C, or tuberculosis infection
- Recent chemotherapy, radiotherapy, or immunosuppressive therapy within 30 days (with corticosteroid exceptions)
- Clinically significant abnormal lab values
- Failure to thrive defined as dropping 20 percentiles in body weight in past 3 months
- Underlying immune function defects
- History of multiple severe life-threatening infections
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
J
Jean M Johnston
CONTACT
C
Cynthia J Tifft, M.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here