Intraneural Administration of scAAV9/JeT-GAN Into the Vagus Nerve for Patients With Giant Axonal Neuropathy (GAN)

Plain-language summary

This Phase 1 study examines the gene therapy scAAV9/JeT-GAN in giant axonal neuropathy (GAN), a rare progressive disorder caused by mutations in the GAN gene. Participants who previously received the drug intrathecally will receive a single dose injected directly into the left vagus nerve, to target autonomic nervous system symptoms; the aim is to evaluate the safety and tolerability of this approach. Participants must have genetically confirmed pathogenic variants in the GAN gene, signs of autonomic dysfunction, and must have completed 5 years of follow-up after their prior intrathecal treatment.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Recruiting

Sponsor

University of Texas Southwestern Medical Center

Intervention

scAAV9/JeT-GAN

Start date

3/1/2026

Estimated completion

6/30/2032

Countries

United States

Related genes

Locations

• Dallas, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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