Aspartylglucosamidase (AGA) Deficiency, Aspartylglucosaminuria
Conditions
Keywords
Aspartylglucosaminuria, AAV9, Aspartylglucosaminuria (AGU), Aspartylglucosamidase (AGA) Deficiency
Brief summary
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).
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.
Interventions
GENETICscAAV9/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
Sponsors
Rare Trait Hope
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Three age-stratified cohorts (1. 18+ years of age; 2. 12-17; 3. 4-11), with optional expansion.
Eligibility
Sex/Gender
ALL
Age
4 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of a single dose of scAAV9/AGA in participants with aspartylglucosaminuria (AGU) | Through Day 720 | Incidence, severity, and causality of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and adverse events of special interest (AESIs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biologic activity following a single dose of scAAV9/AGA in participants with aspartylglucosaminuria (AGU) | Days 360 and 720 | Change from baseline in glycoasparagine (GlcNAc-Asn) levels and Change from baseline in AGA enzyme activity |
| Preliminary efficacy following a single dose of scAAV9/AGA in participants with aspartylglucosaminuria (AGU) | Days 360 and 720 | Change from baseline in functional parameters (NIH Toolbox Motor Function assessments) |
Contacts
CONTACTClinical Director
Outcome results
None listed