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Trial record 1 of 10 for:    GM1 Gangliosidosis
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Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients

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ClinicalTrials.gov Identifier: NCT04041102
Recruitment Status : Recruiting
First Posted : August 1, 2019
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
Passage Bio, Inc.
Information provided by (Responsible Party):
University of Pennsylvania

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. A natural history data set to assess disease progression, particularly in the infantile population, and to explore potential efficacy endpoints and biomarkers for future clinical trials would benefit both the scientific and patient communities. 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. The procedures/interactions include: physical & neurological exam, blood & urine sample collection, questionnaires & assessments of development, ECHO, ECG, x-ray and ultrasound (if MRI not performed). Optional procedures include: EEG, general anesthesia (for MRI and LP), MRI and lumbar puncture (spinal tap).

Condition or disease
GM1 Gangliosidosis

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients
Estimated Study Start Date : January 31, 2020
Estimated Primary Completion Date : February 28, 2024
Estimated Study Completion Date : February 28, 2024


Group/Cohort
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.



Primary Outcome Measures :
  1. Survival (Infantile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]
    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.

  2. Presence of and dependence on feeding tube (Infantile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]
    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.

  3. Change from baseline in standard scores for each domain on the Vineland-II (Juvenile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]
    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.

  4. Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Juvenile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]

    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.



Secondary Outcome Measures :
  1. Survival (Juvenile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]
    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.

  2. Presence of and dependence on feeding tube (Juvenile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]
    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.

  3. Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Infantile GM1 population) [ Time Frame: Baseline through 36 months (3 years) ]

    See these outcome measures described above for full details.

    The BSID-III or the KABC-II 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 juvenile (Type 2) GM1 population and a secondary outcome measure for the infantile (Type 1) GM1 population.


  4. Change from baseline in the PedsQL total score [ Time Frame: Baseline through 36 months (3 years) ]
    The Pediatric Quality of Life Inventory, Version 4.0 (PedsQL) is a 21 to 45-item assessment of quality of life over the previous 30 days, based on parent/caregiver report. The inventory consists of assessments for infants, toddlers, young children, children, teens and young adults, based on the age of the subject. A lower total score indicates higher quality of life.

  5. Change from baseline in attainment and/or retention of six WHO motor development milestones [ Time Frame: Baseline through 36 months (3 years) ]
    Motor development will be assessed in terms of six developmental milestones: sitting without support, standing with assistance, hands-and-knee crawling, walking with assistance, standing alone, and walking alone. Each milestone will be assessed as either "achieved", "not achieved" or "achieved but lost" based on clinician observation as well as parent report.

  6. Onset of and/or change in seizure activity over time [ Time Frame: Baseline through 36 months (3 years) ]
    The change from baseline in presence/absence of seizures and frequency of seizures (if applicable) will be examined through review of seizure diaries recorded by parents over a three year period.

  7. Change from baseline ECG [ Time Frame: Baseline through 36 months (3 years) ]
    An electrocardiogram (ECG) is a test using electrodes attached to the subject's chest, arms, and legs to record the electrical activity in the heart and detect abnormalities. The clinician will note whether each ECG is normal or abnormal, and the results will be compared to the baseline ECG and tracked over time.

  8. Change from baseline in bony structures of the spine using X-ray [ Time Frame: Baseline through 36 months (3 years) ]
    A lateral spine plain film involves taking an X-ray of the subject's spine to determine if there are structural abnormalities. An X-ray of the spine will be performed at the baseline visit, then every 6 months for up to three years in order to assess changes.

  9. Change from baseline in ECHO parameters over time [ Time Frame: Baseline through 36 months (3 years) ]
    An echocardiogram (ECHO) uses ultrasound to produce images of the subject's heart. The ECHO report will be evaluated for changes from baseline through the course of the study.

  10. (OPTIONAL) Change from baseline EEG [ Time Frame: Baseline through 36 months (3 years) ]
    An electroencephalogram (EEG) is a test using electrodes attached to the subject's scalp to detect abnormal activity in the brain. The EEG should be performed, if consent if provided, at each visit. The clinician will note whether each ECG is normal or abnormal, and the results will be compared to the baseline ECG and tracked over time.

  11. (OPTIONAL) Change from baseline in brain volume and volume of substructures measured using MRI [ Time Frame: Baseline through 36 months (3 years) ]
    If consent if provided, magnetic resonance imaging (MRI) of the brain will be obtained, without contrast, to examine changes in the total volume of the brain as well as the volumes of several brain substructures over time. The MRI may be performed under general anesthesia in this pediatric population. It is important that all procedures requiring general anesthesia are performed in close temporal proximity, while the subject is under anesthesia.

  12. (OPTIONAL) Change from baseline in liver and spleen volume measured using MRI [ Time Frame: Baseline through 36 months (3 years) ]
    If consent if provided, magnetic resonance imaging (MRI) of the abdomen will be obtained, without contrast, to examine changes in the total volume of the liver and spleen over time. The MRI may be performed under general anesthesia in this pediatric population. It is important that all procedures requiring general anesthesia are performed in close temporal proximity, while the subject is under anesthesia.

  13. (OPTIONAL) Change from baseline in liver and spleen volume measured using ultrasound [ Time Frame: Baseline through 36 months (3 years) ]
    Only if consent is not provided to obtain images of the abdomen via MRI, an abdominal ultrasound will be performed to examine changes in the total volume of the liver and spleen over time.


Other Outcome Measures:
  1. Exploratory analysis of beta-galactosidase enzyme activity and change over time [ Time Frame: Baseline through 36 months (3 years) ]

    Blood and, if consent is given, cerebrospinal fluid (CSF)* will be collected at the baseline visit and each subsequent visit to analyze beta-galactosidase enzyme activity. The aim is to examine enzyme activity variability, change from baseline and relationship to disease progression. As this biomarker are currently under study, ranges cannot be provided at this time. Additional samples may also be stored at a biobank for future research and testing, if consent is obtained.

    *Collection of CSF via a lumbar puncture is an OPTIONAL procedure conducted only at Baseline and Months 6, 12, 24 and 36.


  2. Exploratory analysis of hexosaminidase enzyme activity and change over time [ Time Frame: Baseline through 36 months (3 years) ]

    Blood and, if consent is given, cerebrospinal fluid (CSF)* will be collected at the baseline visit and each subsequent visit to analyze hexosaminidase enzyme activity. The aim is to examine enzyme activity variability, change from baseline and relationship to disease progression, if applicable. As this biomarker are currently under study, ranges cannot be provided at this time. Additional samples may also be stored at a biobank for future research and testing, if consent is obtained.

    *Collection of CSF via a lumbar puncture is an OPTIONAL procedure conducted only at Baseline and Months 6, 12, 24 and 36.


  3. Exploratory analysis of keratan sulfate levels and change over time [ Time Frame: Baseline through 36 months (3 years) ]
    Blood and urine will be collected at the baseline visit and each subsequent visit to analyze keratan sulfate levels. The aim is to examine variability and change from baseline in the levels as well as relationship to disease progression, if applicable. As this biomarker are currently under study, ranges cannot be provided at this time. Additional samples may also be stored at a biobank for future research and testing, if consent is obtained.

  4. Exploratory analysis of GM1 ganglioside levels and change over time [ Time Frame: Baseline through 36 months (3 years) ]

    If consent is given, cerebrospinal fluid (CSF)* will be collected at the baseline visit and each subsequent visit to analyze GM1 ganglioside levels. The aim is to examine variability and change from baseline in the levels as well as relationship to disease progression. As this biomarker are currently under study, ranges cannot be provided at this time. Additional samples may also be stored at a biobank for future research and testing, if consent is obtained.

    *Collection of CSF via a lumbar puncture is an OPTIONAL procedure conducted only at Baseline and Months 6, 12, 24 and 36.



Biospecimen Retention:   Samples With DNA
The protocol includes the OPTIONAL collection and biobank storage of several biofluid samples for future research. The samples include whole blood, plasma/serum, cerebrospinal fluid (CSF), urine and a dry blood spot card.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with a diagnosis of infantile (Type 1) or juvenile (Type 2) GM1 gangliosidosis.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04041102


Contacts
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Contact: Jess Conicelli 215-746-7042 jessica.conicelli@pennmedicine.upenn.edu
Contact: Jill MacDougall 215-746-2704

Locations
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United States, California
UCSF Benioff Children's Hospital Oakland Not yet recruiting
Oakland, California, United States, 94610
Contact: Jennifer Ferguson         
Principal Investigator: Caroline Hastings, MD         
Sub-Investigator: Paul Harmatz, MD         
United States, Minnesota
University of Minnesota Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Amy Hanson         
Principal Investigator: Jeanine Jarnes, PharmD         
Principal Investigator: Chester Whitley, PhD, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Bianca Ferreira         
Principal Investigator: Can Ficicioglu, MD, PhD         
Brazil
Hospital de Clínicas de Porto Alegre Not yet recruiting
Porto Alegre, Brazil
Contact: Diane Pedrini         
Principal Investigator: Roberto Giugliani, MD, PhD         
Canada, Quebec
Montreal Children's Hospital Research Institute - McGill University Not yet recruiting
Montreal, Quebec, Canada
Contact: Aaron Spahr         
Principal Investigator: Genevieve Bernard, MD         
Turkey
Gazi University Not yet recruiting
Ankara, Turkey
Contact: Tuğçe Inal         
Principal Investigator: Fatih Ezgü, MD         
United Kingdom
UCL Great Ormond Street Institute of Child Health Recruiting
London, United Kingdom
Contact: Christopher Jackson         
Principal Investigator: Julien Baruteau, MD, PhD         
Sponsors and Collaborators
University of Pennsylvania
Passage Bio, Inc.
Investigators
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Principal Investigator: Can Ficicioglu, MD, PhD Children's Hospital of Philadelphia

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04041102    
Other Study ID Numbers: ODC-NHS-GM1-001
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Pennsylvania:
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
Additional relevant MeSH terms:
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Gangliosidoses
Gangliosidosis, GM1
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
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders