A Natural History Study of Aspartylglucosaminuria (AGU)

• ClinicalTrials.gov Identifier: NCT03853876
• Recruitment Status: Suspended
• First Posted: February 26, 2019
• Last Update Posted: August 27, 2019
• Sponsor: Neurogene, Inc.
• Information provided by (Responsible Party): Neurogene, Inc.

Tracking Information

• First Submitted Date: January 17, 2019
• First Posted Date: February 26, 2019
• Last Update Posted Date: August 27, 2019
• Actual Study Start Date: April 18, 2019
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2019)

• Neuropsychological Testing [ Time Frame: 5 years ]
  Participants will undergo a standardized neuropsychological evaluation every 6-12 months, depending upon the assessments as follows: Global Cognitive: Leiter International Performance Scale, 3rd Ed, Reynolds Intellectual Assessment Scales, 2nd Ed, Mullen Scales of Early Learning Emotional: Aberrant Behavior Checklist, 2nd Ed, Behavior Assessment System for Children, 3rd Ed Behavioral functioning: Aberrant Behavior Checklist, 2nd Ed, Behavior Assessment System for Children, 3rd Ed
• Ophthalmological Evaluation [ Time Frame: 5 years ]
  Participants will undergo an ophthalmological assessment every 6 months to better characterize the involvement of the eye in AGU.
• Visual Evoked Potential (VEP) [ Time Frame: 5 years ]
  Participants will undergo a VEP test every 6 months to evaluate electrical signal transmission through the visual pathway from the retina to the visual cortex.
• Brainstem Auditory Evoked Response (BAER) [ Time Frame: 5 years ]
  Participants will undergo a BAER test every 6 months to evaluate electrical signal transmission from the 8th cranial nerve to the brainstem and the cortex in response to certain tones.
• Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS) [ Time Frame: 5 years ]
  An MRI scan of the brain will be performed annually to characterize the structural abnormalities associated with AGU. MRS will be performed on regions of interest in the brain.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03853876 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 21, 2019)

• Adaptive functioning: Vineland Adaptive Behavior Scales, 3rd Ed [ Time Frame: 5 years ]
  Participants will undergo a standardized neuropsychological evaluation every 6-12 months
• Language: Expressive One-Word Picture Vocabulary Test, 4th Ed, Receptive One-Word Picture Vocabulary Test, 4th Ed, NEPSY, 2nd Ed [ Time Frame: 5 years ]
  Participants will undergo a standardized neuropsychological evaluation every 6-12 months
• Motor: NIH Toolbox Early Childhood Motor Battery or NIH Toolbox Motor Battery, 6 Minute Walk Test, Beery-Buktenica Development [ Time Frame: 5 years ]
  Participants will undergo a standardized neuropsychological evaluation every 6-12 months

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Natural History Study of Aspartylglucosaminuria
• Official Title: A Natural History Study of Aspartylglucosaminuria

Brief Summary

Aspartylglucosaminuria (AGU) is a rare neurodegenerative lysosomal storage disease (LSD) characterized by developmental delay, psychomotor regression, worsening intellectual disability, gait disturbance and, ultimately, premature death, and has no available treatments.

The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with AGU. This natural history study is important to better understand disease course to be able to determine clinically meaningful outcome measures for use in future clinical trials.

Detailed Description

Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases caused by a genetic mutation resulting in deficiency or absence of a critical enzyme, leading to the accumulation of toxic deposits in cells across multiple organ systems.

Aspartylglucosaminuria (AGU) is a rare, neurodegenerative, LSD, caused by a deficiency of the aspartylglucosaminidase (AGA) enzyme, which leads to toxic accumulation of aspartylglucosamine and subsequent cellular dysfunction. AGU has been most commonly reported in people of Finnish and Nordic descent, but is present across ethnicities and is typically misdiagnosed or undiagnosed.

Aspartylglucosaminuria (AGU) is characterized by developmental delay and intellectual disability that worsens with age. Early disease is characterized by increased frequency of bacterial ear infections, recurrent ear tube placement, intestinal dysfunction, disruptive sleep patterns, skeletal abnormalities, and gait disturbances, among others. Individuals progressively lose motor and cognitive skills, develop behavioral/emotional lability and their risk of seizures increases with age. People with AGU have a shortened life span.

No prospective natural history study for AGU has been reported. This study aims to prospectively investigate the natural history of AGU, and concurrently to identify potential outcome measures that could be used in future clinical trials. No investigational product will be provided in the study.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   None Retained

Description:

Patients will also be given the opportunity to have serum samples stored for up to 10 years for future exploratory analyses.

• Sampling Method: Non-Probability Sample
• Study Population: Patients with a confirmed genetic diagnosis of aspartylglucosaminuria.

Condition

• Aspartylglucosaminuria
• Aspartylglucosamidase (AGA) Deficiency
• Lysosomal Storage Diseases

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: February 21, 2019): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must have a diagnosis of AGU based on clinical presentation and genetic testing (known or suspected pathogenic mutation in AGA gene).

Exclusion Criteria:

• Patients unable to travel to UT Southwestern Medical Center and Children's Health Dallas will not be enrolled in the prospective natural history study collecting standardized clinical data; however, with participant consent, medical records will be obtained, reviewed, and recorded in the natural history database over time.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03853876
• Other Study ID Numbers: STU 2018-0017
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Neurogene, Inc.
• Study Sponsor: Neurogene, Inc.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kimberly Goodspeed, MD; UT- Southwestern

• PRS Account: Neurogene, Inc.
• Verification Date: August 2019