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

An Open-Label, Single Center, Phase 1/2 Study to Evaluate the Safety and Efficacy of DANAGALEX (scAAV9/AGA) in Participants With Aspartylglucosaminuria (AGU)

The goal of this clinical trial is to learn if the treatment is a safe, tolerable, and efficacious treatment for adults and children with Aspartylglucosaminuria (AGU).

Study Overview

• Status: Not yet recruiting
• Conditions: Aspartylglucosaminuria; Aspartylglucosamidase (AGA) Deficiency
• Intervention / Treatment: Genetic: scAAV9/AGA

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Director; Phone Number: 504-408-1126; Email: clinical@raretrait.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Cohort 1: 18+ years old, Cohort 2: 12-17 years old, then Cohort 3: 4-11 years old	Genetic: scAAV9/AGA; Danagalex, a self-complementary adeno-associated Virus Serotype 9 (AAV9) vector-mediated gene transfer of codon optimized human AGA gene, administered via intrathecal injection; Other Names: Danagalex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of a single dose of scAAV9/AGA in participants with aspartylglucosaminuria (AGU)	Incidence, severity, and causality of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and adverse events of special interest (AESIs)	Through Day 720

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biologic activity following a single dose of scAAV9/AGA in participants with aspartylglucosaminuria (AGU)	Change from baseline in glycoasparagine (GlcNAc-Asn) levels and Change from baseline in AGA enzyme activity	Days 360 and 720
Preliminary efficacy following a single dose of scAAV9/AGA in participants with aspartylglucosaminuria (AGU)	Change from baseline in functional parameters (NIH Toolbox Motor Function assessments)	Days 360 and 720

Collaborators and Investigators

• Sponsor: Rare Trait Hope

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2032

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: AAV9; Aspartylglucosaminuria; Aspartylglucosaminuria (AGU); Aspartylglucosamidase (AGA) Deficiency
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lysosomal Storage Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Aspartylglucosaminuria; Aspartylglucosamidase (AGA) deficiency
• Other Study ID Numbers: 2013-AGU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No