Clinical trial NCT04041102: Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients
Official title: Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Passage Bio, Inc.
First posted: 2019-08-01
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with a diagnosis of infantile (Type 1) or juvenile (Type 2) GM1 gangliosidosis.

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).


Eligibility criteria: Inclusion Criteria:

1. Documentation/ Confirmation of reduced beta-galactosidase enzyme activity in leukocytes
2. Confirmed diagnosis of infantile or juvenile GM1 gangliosidosis with documentation of GLB1 mutations
3. Parent/Caregiver capable of providing informed consent (if cognitively able, child to provide assent as well)
4. 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)
5. 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)

Exclusion Criteria:

1. Enrollment in any other clinical study with an investigational product/ therapy (patients receiving miglustat off-label will be eligible)
2. 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
3. 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

Primary outcomes:
measure: Survival (Infantile GM1 population)
timeFrame: Baseline through 36 months (3 years)
measure: Presence of and dependence on feeding tube (Infantile GM1 population)
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in standard scores for each domain on the Vineland-II (Juvenile GM1 population)
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Juvenile GM1 population)
timeFrame: Baseline through 36 months (3 years)
Secondary outcomes:
measure: Survival (Juvenile GM1 population)
timeFrame: Baseline through 36 months (3 years)
measure: Presence of and dependence on feeding tube (Juvenile GM1 population)
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Infantile GM1 population)
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in the PedsQL total score
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in attainment and/or retention of six World Health Organization motor development milestones
timeFrame: Baseline through 36 months (3 years)
measure: Onset of and/or change in seizure activity over time
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline ECG
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in bony structures of the spine using X-ray
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in ECHO parameters over time
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline EEG
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in brain volume and volume of substructures measured using MRI
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in liver and spleen volume measured using MRI
timeFrame: Baseline through 36 months (3 years)
measure: Change from baseline in liver and spleen volume measured using ultrasound
timeFrame: Baseline through 36 months (3 years)
Other outcomes:
measure: Exploratory analysis of beta-galactosidase enzyme activity and change over time
timeFrame: Baseline through 36 months (3 years)
measure: Exploratory analysis of hexosaminidase enzyme activity and change over time
timeFrame: Baseline through 36 months (3 years)
measure: Exploratory analysis of keratan sulfate levels and change over time
timeFrame: Baseline through 36 months (3 years)
measure: Exploratory analysis of GM1 ganglioside levels and change over time
timeFrame: Baseline through 36 months (3 years)
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Montreal
country: Canada
facility: Montreal Children's Hospital Research Institute - McGill University
state: Quebec
city: Ankara
country: Turkey
facility: Gazi University
city: London
country: United Kingdom
facility: UCL Great Ormond Street Institute of Child Health
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Can Ficicioglu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: