NCT05317780

Canavan-Single Patient IND

NO LONGER AVAILABLE Last updated 23 August 2023

What this trial tests

trial testing rAAV9-CB6-AspA in Canavan Disease. No longer available.

Quick facts

Lead sponsor	University of Florida
Status	NO LONGER AVAILABLE
Study type	EXPANDED_ACCESS
Sites	1 location across United States

Drugs / interventions tested

• rAAV9-CB6-AspA — full drug profile →

Conditions studied

• Canavan Disease — all drugs for Canavan Disease →

Sponsor

University of Florida

Who can join

Adults 18 Months to 24 Months, male only, with Canavan Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

A recombinant virus vector constructed from adeno-associated virus (AAV) has been engineered to carry the human aspartoacylase (ASPA) gene expressed from a modified CMV-enhancer chicken β-actin (CB6) promoter. The construct has been shown to produce ASPA in animal models of Canavan disease, which closely match the proposed human study. The proposed clinical trial is an open label, expanded access study administering rAAV9-CB6-AspA gene vector by simultaneous systemic and intracerebroventricular routes to a single human subject (18-24 months of age) with Canavan disease. The subject will also receive immune modulation to transiently ablate B-cells (Rituximab) and modulate T-cell response (Sirolimus) prior to the initial exposure to AAV9. Given the null AspA mutations of the subject and current AAV seronegative status, this regimen will allow for later exposure to the therapeutic vector if needed and block any immuno-toxicity in the CNS. The goal of this study is to measure the safety and efficacy of AAV-mediated gene therapy as a treatment approach for neuronal pathology in Canavan disease. The subject will act as their own control and change from baseline will be assessed in regards to levels of brain NAA, brain water content and morphology, improved clinical status and peripheral levels of NAA. Safety parameters measured in this study will include: serum chemistries and hematology, urinalysis, physical assessments, whole blood assay for vector genomes, immunologic response to ASPA and AAV, as well as reported subject symptom history.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current clinical applications of AAV-mediated gene therapy.
   Byrne BJ, Flanigan KM, Matesanz SE, Finkel RS, et al · · 2025 · cited 43× · PMID 40329530 · DOI 10.1016/j.ymthe.2025.04.045
2. Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants.
   Grønbæk-Thygesen M, Voutsinos V, Johansson KE, Schulze TK, et al · · 2024 · cited 31× · PMID 38740822 · DOI 10.1038/s41467-024-48481-0
3. A versatile toolkit for overcoming AAV immunity.
   Li X, Wei X, Lin J, Ou L. · · 2022 · cited 31× · PMID 36119036 · DOI 10.3389/fimmu.2022.991832
4. Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.
   Xu L, Yao S, Ding YE, Xie M, et al · · 2024 · cited 17× · PMID 39334366 · DOI 10.1186/s12967-024-05661-2
5. Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.
   Zhou L, Wang Y, Xu Y, Zhang Y, et al · · 2024 · cited 12× · PMID 39559557 · DOI 10.1016/j.omtm.2024.101357
6. Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.
   Metovic J, Li Y, Gong Y, Eichler F. · · 2024 · cited 12× · PMID 39276676 · DOI 10.1016/j.neurot.2024.e00443
7. Virus-Based Biological Systems as Next-Generation Carriers for the Therapy of Central Nervous System Diseases.
   Nowak I, Madej M, Secemska J, Sarna R, et al · · 2023 · cited 11× · PMID 37514117 · DOI 10.3390/pharmaceutics15071931
8. The potential of gene delivery for the treatment of traumatic brain injury.
   Dooley J, Hughes JG, Needham EJ, Palios KA, et al · · 2024 · cited 3× · PMID 39069631 · DOI 10.1186/s12974-024-03156-x