Gene therapy for treating GM1 gangliosidosis
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
This study is testing a new gene therapy to see if it can help people with Type I and Type II GM1 gangliosidosis by delivering a gene that may improve their condition.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 54 (estimated) |
| Ages | 6 Months to 12 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT03952637 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and efficacy of a gene therapy using an AAV9 vector to deliver the human Beta-galactosidase gene to patients with Type I and Type II GM1 gangliosidosis. Participants will undergo a series of medical evaluations and tests, including blood tests, EEGs, and MRIs, to assess their condition before and after treatment. The trial is designed to administer varying doses of the gene transfer agent to determine the optimal dosage and monitor for any adverse effects. The study will take place at the National Institutes of Health Clinical Center over an 8-10 week period.
Who should consider this trial
Good fit: Ideal candidates include infants and young children diagnosed with Type I or Type II GM1 gangliosidosis who meet specific genetic and health criteria.
Not a fit: Patients who do not have biallelic mutations in the GLB1 gene or those with antibody titers above the specified threshold may not benefit from this study.
Why it matters
Potential benefit: If successful, this gene therapy could provide a much-needed treatment option for patients suffering from GM1 gangliosidosis, potentially improving their symptoms and quality of life.
How similar studies have performed: While gene therapy for lysosomal diseases is a novel approach, similar studies have shown promise in treating other genetic disorders, indicating potential for success in this area.
Eligibility criteria
Show full inclusion / exclusion criteria
* INCLUSION CRITERIA:
Type I subjects
* Male or female subjects \>= 6 months old and \<= 12 months old at time of full ICF signing
* Biallelic mutations in GLB1
* Documented deficiency of Beta-galactosidase enzyme by clinical laboratory testing
* Phenotype consistent with a diagnosis of Type I GM1 gangliosidosis
* Symptomatic subjects: as determined by the opinion of the Principal Investigator and based on the criteria set forth by Brunetti-Pierri et al:
* Age of symptom onset \<= 6 months of age
* Rapidly progressive with developmental delay and hypotonia
* Pre- symptomatic subjects: must have mutations confirmed to be associated with the Type I subtype
* AAV9 antibody titers \<=1:50
* Agree to reside within 50 miles of the study site for at least 1 month following treatment
Type II subjects
* Vineland-3 Adaptive Behavior composite standard score greater than or equal to 40
* Male or female subjects \> 6 months old and \< 12 years old at time of full ICF signing
* Biallelic mutations in GLB1
* Documented deficiency of beta-galactosidase enzyme by clinical laboratory testing
* Phenotype consistent with a diagnosis of Type II GM1 gangliosidosis, with symptom onset after the first year of life
* AAV9 antibody titers \<=1:50
* Agree to reside within 50 miles of the study site for at least 1 month following treatment
EXCLUSION CRITERIA:
* AAV9 antibody titers \>1:50
* Contraindications to concomitant medications
* Serious illness that would not allow travel to the study site
* Unwilling to undergo study interventions as outlined in the Schedule of Events
* Subjects receiving other unapproved, off-label or experimental therapies for GM1 gangliosidosis (i.e. miglustat, Tanganil) within the last 60 days
* Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
* Pregnant or lactating subjects
* Immunizations of any kind in the month prior to screening
* Evidence of cardiomyopathy on history, exam, or additional testing (echocardiogram or electrocardiogram) or other cardiac disease that in the opinion of the investigator would deem the subject unsafe to participate in the trial
* Indwelling ferromagnetic devices that would preclude MRI/fMRI/MRS imaging
* Ongoing medical condition that is deemed by the Principal Investigator to interfere with the conduct or assessments of the study
* History of infection with human immunodeficiency virus (HIV), hepatitis A, B, or C, or tuberculosis.
* History of or current chemotherapy, radiotherapy or other immunosuppressive therapy within the past 30 days. Corticosteroid treatment may be permitted at the discretion of the PI
* Abnormal laboratory values considered clinically significant per the investigator
* Failure to thrive, defined as:
\-- Falling 20 percentiles (20/100) in body weight in the 3 months preceding Screening/Baseline
* Underlying defect in immune function
* History of multiple and severe life-threatening infections
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Cynthia J Tifft, M.D. — National Human Genome Research Institute (NHGRI)
- Study coordinator: Jean M Johnston
- Email: johnstonjm@mail.nih.gov
- Phone: (240) 515-1448
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.