A Phase I/II Open-label Intraneural Administration of scAAV9/JeT-GAN Into the Vagus Nerve to Determine the Safety and Efficacy for Patients With Giant Axonal Neuropathy (GAN) Caused by a Mutation in the GAN Gene
University of Texas Southwestern Medical Center
Summary
Giant axonal neuropathy (GAN) is a rare pediatric disorder caused by autosomal recessive mutations in the GAN gene. GAN is a multisystem, neurodegenerative disorder affecting the peripheral nervous system (PNS), central nervous system (CNS) and autonomic nervous system (ANS). GAN is a fatal disease with many patients not surviving past early adulthood due to aspiration pneumonia and pulmonary complications. Currently, there are no approved drugs or other therapies for the treatment of GAN; and only supportive care therapies exist, leaving an unmet medical need to treat this rare, progressive, and ultimately fatal neurodegenerative disease. The drug used in this study (scAAV9/JeT-GAN) has been studied in a previous gene therapy clinical trial by which the drug was administered as a single injection into the spinal canal (intrathecal \[IT\] administration) to treat the symptoms associated with the CNS and PNS neurodegeneration; however, this administration method did not address the symptoms associated with neurodegeneration of the ANS. To treat the symptoms associated with ANS, this study has been designed to evaluate the safety and tolerability of a single dose of scAAV9/JeT-GAN administered directly into the left vagus nerve (intraneurally) in participants who have previously received scAAV9/JeT-GAN administered intrathecally. This study involves the use of an investigational drug called scAAV9/JeT-GAN "Investigational" means that the drug has not been approved by the U.S. Food \& Drug Administration (FDA) for the treatment of GAN and the progression of neurodegeneration to the CNS, PNS and ANS. This is the first study in humans to administer the drug directly into the left vagus nerve. We want to find out what effects, good and/or bad, scAAV9/JeT-GAN has when administered directly into the vagus nerve. The safety of intrathecal (IT) administration of scAAV9/JeT-GAN has been established in a prior research study; however, the people in this study will be the first people to receive the drug intraneurally. As a result, information about the safety and effectiveness of the route of administration is incomplete and all of the possible side effects are not yet known.
Eligibility
- Age range
- 10–25 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Confirmed diagnosis of GAN disease by: 1. Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or confirmed pathogenic variants in the GAN gene; 2. Clinical history or symptoms to ANS dysfunction. 2. Previously treated with IT AAV/GAN and completion of 5 year follow up prior to enrollment. 3. Parents/l LAR willing to accompany the participant to all study visits and who will provide consent for their child's participation. 4. Subject able to comply with all protocol requirements and procedures. 5. Up to date on childhood…
Interventions
- GeneticscAAV9/JeT-GAN
The drug used in this study (scAAV9/JeT-GAN) has been studied in a previous gene therapy clinical trial by which the drug was administered as a single injection into the spinal canal (intrathecal \[IT\] administration) to treat the symptoms associated with the CNS and PNS neurodegeneration. This is the first study in humans to administer the drug directly into the left vagus nerve.
Location
- Children's HealthDallas, Texas