Safety and Efficacy of scAAV9/AGA Gene Therapy in Participants With Aspartylglucosaminuria (AGU)

This study is a first in human (FIH) open-label study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding aspartylglucosaminidase (AGA) in participants with Aspartylglucosaminuria (AGU). Safety will be monitored continuously throughout the study for adverse / serious adverse events and dose limiting toxicities. All outcomes (primary, secondary, exploratory) will be assessed at 52 and 104 weeks.

Inclusion criteria

• Documented molecular diagnosis of AGU (e.g., whole exome sequencing, whole genome sequencing, gene panel, single-gene sequencing, or chromosomal microarray) identifying two pathogenic and/or likely pathogenic variants in the AGA gene
• The participant, or the participant's parent or legal guardian, is registered in the AGU Natural History Study
• The participant, or the participant's parent, legal guardian, or caregiver are willing and able to travel to the study site and complete all aspects of the study, adhere to the study visit schedule, and comply with all assessments.

Exclusion criteria

• Any prior or ongoing medical condition, clinical history, physical examination finding, cardiovascular or ECG abnormality, or laboratory result that may: (1) place the participant at undue risk during administration; (2) interfere with study treatment or follow-up compliance; or (3) confound the interpretation of study data.
• Acute illness requiring hospitalization within 6 weeks prior to Screening
• Contraindications to or unwillingness to undergo MRI, lumbar puncture (LP) or other study procedures;
• Chronic requirement for respiratory support, including invasive or non-invasive ventilation;
• Known bleeding disorders (e.g., hemophilia, von Willebrand disease) or any medical condition or treatment associated with increased bleeding risk;
• Prior treatment with a gene, cell therapy, or bone marrow replacement;
• Treatment with any investigational product (IP) within 90 days or 5 half-lives of the IP, whichever is longer, prior to screening period;
• Any condition that in the opinion of the investigator or the study medical monitor would prevent the patient from fully complying with the requirements of the study (including the corticosteroid treatment) and/or would impact or interfere with the evaluation and interpretation of patient safety or efficacy results.