RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: GM1 gangliosidosis is a disorder that destroys nerve cells. It is fatal. There is no treatment. People with GM1 are deficient in a certain enzyme. A gene therapy may help the body make this enzyme. This could improve GM1 symptoms. Objective: To test if a gene therapy helps Type I and Type II GM1 gangliosidosis symptoms. Eligibility: Type I subjects will be male and female \>= 6 months \<= 12 months of age at the time of full ICF signing. Type II subjects will be male and female \> 12 months old and \< 12 years old at the time of full ICF signing. Design: Participants will be screened with their medical history and a phone survey. Participants will stay at NIH for 8-10 weeks. Participants will have baseline tests: Blood, urine, and heart tests Hearing tests Ultrasound of abdomen EEG: Sticky patches on the participant s head will measure brain function. Lumbar puncture: A needle will be stuck into the participant s spine to remove fluid. MRI scans, bone x-rays, and bone scans: Participants will lie in a machine that takes pictures of the body IQ tests Neurology exams Central line placement Skin biopsy: A small piece of the participant s skin will be removed. Speech tests Participants will have an x-ray while swallowing food. Participants will take drugs by mouth and IV. This will get their immune system ready for therapy. Participants will get the gene therapy by IV. They may stay at NIH for a week to watch for side effects. Participants will have visits 3 and 6 months after treatment. Then visits will be every 6 months for 2 years. Then they will have a visit at 3 years. Visits will take 4-5 days. Participants will return to NIH once a year for 2 years for tests in an extension study....

Official 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

Quick Facts

Study Start:2019-08-19

Study Completion:2028-01-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03952637

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:6 Months to 12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD

Inclusion Criteria	Exclusion Criteria
* 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 * 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	* 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: * Underlying defect in immune function * History of multiple and severe life-threatening infections

Inclusion Criteria

Exclusion Criteria

* 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
* 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

* 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:
* Underlying defect in immune function
* History of multiple and severe life-threatening infections

Contacts and Locations

Study Contact

Jean M Johnston

CONTACT

(240) 515-1448

johnstonjm@mail.nih.gov

Cynthia J Tifft, M.D.

CONTACT

(301) 451-8485

cynthiat@mail.nih.gov

Principal Investigator

Cynthia J Tifft, M.D.

PRINCIPAL_INVESTIGATOR

National Human Genome Research Institute (NHGRI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Human Genome Research Institute (NHGRI)

Cynthia J Tifft, M.D., PRINCIPAL_INVESTIGATOR, National Human Genome Research Institute (NHGRI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-08-19

Study Completion Date2028-01-01

Study Record Updates

Study Start Date2019-08-19

Study Completion Date2028-01-01

Terms related to this study

Keywords Provided by Researchers

Lysosomal Diseases

Additional Relevant MeSH Terms

Lysosomal Diseases
Gangliosidosis
GM1