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

Launched by NATIONAL HUMAN GENOME RESEARCH INSTITUTE (NHGRI) · May 15, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a new gene therapy for GM1 gangliosidosis, a serious condition that affects the nervous system and currently has no treatment. The therapy aims to help patients produce a missing enzyme, potentially improving their symptoms. The trial is open to children with Type I GM1 gangliosidosis who are between 6 and 12 months old, and to children with Type II GM1 who are between 1 and 12 years old. To qualify, participants must have specific genetic mutations and a confirmed deficiency in the enzyme beta-galactosidase.

If a child joins the study, they will stay at the National Institutes of Health (NIH) for about 8-10 weeks and undergo various tests to assess their health, including blood tests, brain scans, and hearing evaluations. After preparing their immune system with medications, participants will receive the gene therapy through an IV. They will be monitored for side effects and will have follow-up visits at 3 and 6 months after treatment, then every 6 months for the next two years, and then again at three years. This study represents a hopeful step towards finding a treatment for GM1 gangliosidosis, but participation involves a commitment to regular visits and tests.

Gender

ALL

Eligibility 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