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

• Register: ClinicalTrials.gov
• Last refreshed on: 29 January 2024
• Main ID: NCT03952637
• Date of registration: 15/05/2019
• Prospective Registration: Yes
• Primary sponsor: National Human Genome Research Institute (NHGRI)
• Public 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
• Scientific 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
• Date of first enrolment: August 19, 2019
• Target sample size: 45
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03952637
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Jean M Johnston

• Name: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

• Name: Cynthia J Tifft, M.D.
• Affiliation: National Human Genome Research Institute (NHGRI)

Key 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, 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



Age minimum: 6 Months
Age maximum: 12 Years
Gender: All

Health Condition(s) or Problem(s) studied

Gangliosidosis

GM1

Lysosomal Diseases

Intervention(s)

Biological: AAV9-GLB1

Drug: Sirolimus

Procedure: Abdominal ultrasound

Procedure: Speech and modified barium swallow study

Procedure: Brain MRI/MRS/fMRI

Procedure: Skin biopsy

Behavioral: PICC or other Central line placement

Drug: Methylprednisolone

Diagnostic Test: Audiology assessment with ABR

Diagnostic Test: Echocardiogram

Other: Neurology exam

Procedure: Lumbar puncture

Behavioral: Neurocognitive testing

Diagnostic Test: Bone density scan (DEXA)

Procedure: Skeletal survey

Procedure: Ophthalmology exam

Diagnostic Test: Laboratory tests

Drug: Prednisone

Diagnostic Test: Electrocardiogram (EKG)

Drug: Rituximab

Other: Electroencephalogram (EEG) awake and extended overnight

Primary Outcome(s)

Safety [Time Frame: Several time points over 3 years]

Secondary Outcome(s)

Brain MRI/MRS/fMRI [Time Frame: Varies between Type II and Type I subjects.]

Motor function [Time Frame: Varies between Type II and Type I subjects.]

Overall survival [Time Frame: Throughout study]

Developmental changes [Time Frame: Varies between Type II and Type I subjects.]

CGI scale [Time Frame: Several timepoints over 3 years]

Neurological function [Time Frame: Several timepoints over 3 years]

Secondary ID(s)

190101

19-HG-0101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Sio Gene Therapies