Vagus nerve gene therapy (scAAV9/JeT-GAN) for giant axonal neuropathy

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

This Phase 1 test delivers a gene therapy (scAAV9/JeT-GAN) directly into the vagus nerve to see if it can help people with confirmed giant axonal neuropathy who previously received intrathecal AAV/GAN.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 4 (estimated)
• Ages: 10 Years to 25 Years
• Sex: All
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT07543991 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label study delivers a single intraneural injection of scAAV9/JeT-GAN into the vagus nerve to target autonomic and peripheral nervous system involvement in GAN. Enrollment is limited to individuals with genetically confirmed GAN who have completed five years of follow-up after prior intrathecal AAV/GAN treatment. Participants will be closely monitored for safety, autonomic and respiratory function changes, and biological markers of gene delivery. The trial is conducted at the University of Texas Southwestern/Children's Health site in Dallas, Texas.

Who should consider this trial

Good fit: Ideal candidates are individuals with genetically confirmed GAN who completed a prior intrathecal AAV/GAN treatment and the required five-year follow-up, are medically able to undergo the procedure, and have a parent or legal guardian available to provide consent and attend visits.

Not a fit: People without a confirmed GAN genetic diagnosis, those who have not previously received intrathecal AAV/GAN with the required follow-up, or those with medical conditions that preclude vagus nerve injection are unlikely to be eligible or benefit.

Why it matters

Potential benefit: If successful, this approach could improve autonomic control and reduce life-threatening respiratory and swallowing complications in people with GAN.

How similar studies have performed: A prior intrathecal scAAV9/JeT-GAN trial delivered gene therapy to the CNS/PNS and showed biological activity, but direct vagus nerve (intraneural) delivery to target autonomic function is a novel approach with limited human data.

Eligibility criteria

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 vaccinations according to Centers for Disease Control (CDC) guidelines. Annual influenza and COVID-19 vaccinations are highly recommended.
6. Female participants of child-bearing potential must have a negative urine and/or negative serum pregnancy test at screening/baseline; (a) Female participants must agree to use an effective form of birth control during study participation.

Exclusion Criteria:

1. Inability to participate in study procedures (as determined by the site investigator).
2. Inability to be safely sedated in the opinion of the clinical anesthesiologist.
3. Concomitant illness or requirement for chronic drug treatment that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer.
4. The presence of significant non-GAN related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
5. Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than this gene therapy) during the study.
6. Currently participating in another interventional (drug/device) clinical trial.
7. Experienced an SAE (serious adverse event) related to scAAV9/JeT-GAN while participating in the first GAN IT study.
8. Contraindication to scAAV9/JeT-GAN or any of its ingredients.
9. Contraindication to any of the immune suppression medications used in this study.
10. Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy

Where this trial is running

Dallas, Texas

• Children's Health — Dallas, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Samantha Bridges, BSN

Conditions Giant Axonal Neuropathy; Giant axonal neuropathy; Gene Therapy; scAAV9/JeT-GAN; Neurodegenerative disorder; Autonomic Nervous System; Hannah's Hope Fund