Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients

NCT04041102 | Completed

• 1 other identifier: ODC-NHS-GM1-001-01
• Study Type: observational
• Target: 31
• Locations: 5 countries
• Sites: 6

Brief Summary

Owing to the rarity, severity, speed of progression and fatal prognosis of infantile and juvenile GM1, there is a limited understanding of overall disease progression and meaningful outcome measures. This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of GM1 disease progression and clinical outcome. Having a GM1 natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials. This natural history study will follow up to 40 subjects diagnosed with GM1 gangliosidosis (up to 20 infantile (Type 1) and 20 late infantile/juvenile (Type 2)) for up to 3 years. Visits will be conducted every 6 months, during which several procedures will be performed and the data recorded in order to learn about the natural course of the disease, including changes in clinical and neurological assessments and electrophysiologic, imaging and biofluid biomarkers. Study procedures include: physical \& neurological exam, blood \& urine sample collection, questionnaires \& assessments of development, seizure diary, ECHO, ECG, x-ray and ultrasound (if MRI not performed), EEG and genetic testing (if not already done). The following procedures are subject to local/institutional policies and the medical discretion of the Study Physician: MRI, lumbar puncture (spinal tap) and General anesthesia/sedation (for MRI and LP).

Conditions

GM1 Gangliosidosis

Keywords

GM1; GM1 gangliosidosis; GM1 Type 1; GM1 Type 2; GM1 gangliosidosis Type 1; GM1 gangliosidosis Type 2; GM1 natural history study; GM1 gangliosidosis natural history study; Lysosomal Storage Disorders; Lysosomal Disorders

Outcome Measures

Primary Outcomes (4)

• Survival (Infantile GM1 population)

  Survival will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.

  Baseline through 36 months (3 years)

• Presence of and dependence on feeding tube (Infantile GM1 population)

  The presence of a feeding tube and dependence on the feeding tube, if applicable, will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.

  Baseline through 36 months (3 years)

• Change from baseline in standard scores for each domain on the Vineland-II (Juvenile GM1 population)

  The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is a standard assessment for measuring personal and social skills for children and adults (birth through 90 years of age). This assessment aids in diagnosis of intellectual and developmental disabilities or delays associated with a variety of diseases/disorders. The assessment includes 5 domains. Scores for each domain and a composite adaptive behavior score are then converted to standard scores with a range of 20 to 140, with a score of 140 correlating to a high adaptive level.

  Baseline through 36 months (3 years)

• Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Juvenile GM1 population)

  Based on the outcome of the Vineland-II, each subject will be given a developmental age score that will determine whether the Bayley Scale of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II) is administered. Children with a developmental age of 42 months or less will be administered the BSID-III and those with a developmental age of greater than 42 months will be administered the KABC-II. The BSID-III assesses 5 major areas of development. Each domain results in a raw score that is converted to a composite score. A higher composite score generally corresponds with higher function. The KABC-II assesses 4 major areas of intelligence and achievement in young children. Each domain results in a raw score that is converted to a standard score. Scores from 90-109 are generally considered average, with scores higher than 109 considered to be above average.

  Baseline through 36 months (3 years)

Secondary Outcomes (13)

• Survival (Juvenile GM1 population)

  Baseline through 36 months (3 years)

• Presence of and dependence on feeding tube (Juvenile GM1 population)

  Baseline through 36 months (3 years)

• Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Infantile GM1 population)

  Baseline through 36 months (3 years)

• Change from baseline in the PedsQL total score

  Baseline through 36 months (3 years)

• Change from baseline in attainment and/or retention of six World Health Organization motor development milestones

  Baseline through 36 months (3 years)

Other Outcomes (4)

• Exploratory analysis of beta-galactosidase enzyme activity and change over time

  Baseline through 36 months (3 years)

• Exploratory analysis of hexosaminidase enzyme activity and change over time

  Baseline through 36 months (3 years)

• Exploratory analysis of keratan sulfate levels and change over time

  Baseline through 36 months (3 years)

Study Arms (1)

Infantile (Type 1) or Juvenile (Type 2) GM1 Gangliosidosis

This study observes one cohort: up to 40 Infantile GM1 (Type 1) or Juvenile GM1 (Type 2) subjects.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with a diagnosis of infantile (Type 1) or juvenile (Type 2) GM1 gangliosidosis.

You may qualify if:

• Documentation/ Confirmation of reduced beta-galactosidase enzyme activity in leukocytes
• Confirmed diagnosis of infantile or juvenile GM1 gangliosidosis with documentation of GLB1 mutations
• Parent/Caregiver capable of providing informed consent (if cognitively able, child to provide assent as well)
• Infantile (Type 1) GM1 subjects: Documented symptom onset by 6 months of age with significant hypotonia on exam or history elicited from parent(s)/ caregiver(s)
• Juvenile (Type 2) GM1 subjects: Documented symptom onset after 6 months of age OR documented symptom onset prior to 6 months of age without significant hypotonia on exam or elicited from parent(s)/ caregiver(s)

You may not qualify if:

• Enrollment in any other clinical study with an investigational product/ therapy (patients receiving miglustat off-label will be eligible)
• Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or a secondary cause that may, in the opinion of the investigator, confound interpretation of study results
• Any condition that, in the opinion of the investigator, would put the subject at undue risk or make it unsafe for the subject to participate

Sponsors & Collaborators

• University of Pennsylvania: lead
• Passage Bio, Inc.: collaborator

Study Sites (6)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94610, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Location

Montreal Children's Hospital Research Institute - McGill University

Montreal, Quebec, Canada

Location

Gazi University

Ankara, Turkey (Türkiye)

Location

UCL Great Ormond Street Institute of Child Health

London, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

The protocol includes the collection and biobank storage of several biofluid samples for future research. The samples include plasma/serum, cerebrospinal fluid (CSF; optional) and urine.

MeSH Terms

Conditions

Gangliosidosis, GM1; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Gangliosidoses; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Can Ficicioglu, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2019
• First Posted: August 1, 2019
• Study Start: June 12, 2020
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: October 24, 2025

Record last verified: 2025-10

Locations

GB (1); BR (1); TU (1); US (2); CA (1)