Actively Recruiting

Phase 1
Phase 2
Age: 6Months - 12Years
All Genders
ID03952637

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

N/A

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

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 1/2 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

Eligible

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
Not Eligible

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

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - Approximately 3 weeks before gene transfer

Participants undergo immune modulation therapy with rituximab infusions and sirolimus to prepare for gene transfer treatment.

2 infusions before gene transfer plus ongoing medication

Treatment

Duration - Single day for infusion with medication continued up to 3 months or longer as indicated

Participants receive a single intravenous infusion of the gene transfer vector AAV9-GLB1. Methylprednisolone is given prior to infusion, followed by oral prednisone for 3 days. Central line placement occurs to facilitate treatment.

1 infusion visit plus medication and central line placement

Safety Monitoring and Follow-up Assessments

Duration - Up to 3 years

Participants are monitored for safety and treatment effects with regular clinical exams, imaging, laboratory tests, neurological and neurocognitive assessments, and other procedures over several years.

Multiple visits over 3 years including imaging, neurological exams, neurocognitive testing, and laboratory assessments

Trial Site Locations

Total: 1 location

1

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

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Research Team

J

Jean M Johnston

C

Cynthia J Tifft, M.D.

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

2

Frequently Asked Questions

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Published Research Related To This Trial

AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis.

Sichi Liu, Wenhao Ma, Yuyu Feng...

https://pubmed.ncbi.nlm.nih.gov/35249485