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Virus Therapy

AAV9 Vector Gene Therapy for GM1 Gangliosidosis

Phase 1 & 2

Recruiting

Led By Cynthia J Tifft, M.D.

Research Sponsored by National Human Genome Research Institute (NHGRI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Type I subjects: Male or female subjects >= 6 months old and <= 12 months old at time of full ICF signing with biallelic mutations in GLB1 and documented deficiency of Beta-galactosidase enzyme by clinical laboratory testing and phenotype consistent with a diagnosis of Type I GM1 gangliosidosis

Symptomatic subjects: Age of symptom onset <= 6 months of age, rapidly progressive with developmental delay and hypotonia

Must not have

Failure to thrive, defined as falling 20 percentiles (20/100) in body weight in the 3 months preceding Screening/Baseline

History of infection with human immunodeficiency virus (HIV), hepatitis A, B, C or tuberculosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up several timepoints over 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a gene therapy to see if it helps symptoms of GM1 gangliosidosis, a disorder which destroys nerve cells and is fatal. There is no current treatment.

Who is the study for?

This trial is for children with GM1 gangliosidosis, a fatal nerve cell disorder. Type I participants must be 6-12 months old, while Type II can be older than 12 months but younger than 12 years. They should have specific genetic mutations and low immune responses to AAV9 (antibody titers <=1:50). Participants need to stay near the study site post-treatment and cannot have had previous gene therapy or certain medical conditions.

What is being tested?

The trial tests a gene therapy using an AAV9 vector to deliver an enzyme-lacking in GM1 patients. It includes extensive pre-treatment assessments like blood tests, EEGs, MRIs, and cognitive exams. Post-therapy monitoring involves regular check-ups over three years to evaluate the treatment's effectiveness and safety.

What are the potential side effects?

Potential side effects may include reactions related to immune system preparation drugs (like Rituximab), discomfort from procedures such as lumbar puncture or central line placement, MRI-related issues if metal devices are present in the body, and general risks associated with IV treatments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a baby aged 6-12 months with a confirmed diagnosis of Type I GM1 gangliosidosis.

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My symptoms started before I was 6 months old and include rapid progression, developmental delay, and muscle weakness.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have lost a significant amount of weight recently.

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I have a history of HIV, hepatitis A, B, C, or tuberculosis.

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I have had many severe infections that were life-threatening.

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I am not willing to follow the study's required procedures.

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I do not have a serious illness preventing me from traveling to the study site.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ several timepoints over 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~several timepoints over 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and several timepoints over 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety

Secondary study objectives

Brain MRI/MRS/fMRI

CGI scale

Developmental changes

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: 2Experimental Treatment21 Interventions

Following the last Stage 1 subject s 6 months visit, data will be reviewed, and Stage 2 dosing and assessments will be determined. If Stage 2 dosing is to proceed, it will be reflected in a protocol amendment.

Group II: 1Experimental Treatment21 Interventions

In Stage 1, up to 5 Type II subjects will receive 1.5E13 vg/kg of the gene transfer agent, and two Type II subjects will receive 4.5E13 vg/kg of the gene transfer agent. In Stage 1, up to 3 Type I subjects will receive 1.5E13 of the gene transfer agent (Cohort 1) and then up to 3 subjects will receive 4.5E13 of the gene transfer agent (Cohort 2).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Neurocognitive testing

2017

N/A

~70

Abdominal ultrasound

2020

Completed Phase 4

~1240