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

NCT07543991 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STU20250052
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Giant Axonal Neuropathy (GAN)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety of scAAV9/JeT-GAN when delivered to the Vagus Nerve - Based on the Number and Severity of Adverse Events Attributable to Toxicity

  Safety and tolerability will be determine by the number of Incidences of unanticipated treatment-related toxicities, Grade 3 or higher. Toxicity of scAAV9/JeT-GAN i will be determined by the amount of occurrences and severity of serious adverse events (adverse events Grade 4 and 5). Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 details the criteria for classifying adverse events. The requirements for classifying an AE a Grade 3 or higher is the following: Grade 3 Severe: Severe or medically significant but not immediately life- threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL (the ability to care for oneself without assistance). * Grade 4 Life-threatening consequences; urgent intervention indicated. * Grade 5 Death related to AE

  3 years post treatment

Secondary Outcomes (2)

• Stability or Improvement in Autonomic Nervous Symptoms

  3 years post treatment

• Stability or Improvement of Motor Function

  2 Years

Study Arms (1)

Open Label administration of scAAV9/JeT-GAN

EXPERIMENTAL

Patients will receive a single injection of scAAV9/JeT-GAN, given directly into the left vagus nerve. scAAV9/JeT-GAN is an injectable drug that contains optimized human gigaxonin (the protein that is mutated in GAN) DNA. scAAV9/JeT-GAN is delivered to cells through a modified viral vector. The vector is the vehicle that transports the gigaxonin DNA to cells. The vector used to transport gigaxonin DNA, is virus called adeno-associated virus serotype 9 (AAV9); however, this virus has been modified so as not cause an illness or infection.

Genetic: scAAV9/JeT-GAN

Interventions

scAAV9/JeT-GAN GENETIC

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.

Open Label administration of scAAV9/JeT-GAN

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Confirmed diagnosis of GAN disease by:
• Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or confirmed pathogenic variants in the GAN gene;
• Clinical history or symptoms to ANS dysfunction.
• Previously treated with IT AAV/GAN and completion of 5 year follow up prior to enrollment.
• Parents/l LAR willing to accompany the participant to all study visits and who will provide consent for their child's participation.
• Subject able to comply with all protocol requirements and procedures.
• Up to date on childhood vaccinations according to Centers for Disease Control (CDC) guidelines. Annual influenza and COVID-19 vaccinations are highly recommended.
• 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.

You may not qualify if:

• Inability to participate in study procedures (as determined by the site investigator).
• Inability to be safely sedated in the opinion of the clinical anesthesiologist.
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer.
• 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.
• 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.
• Currently participating in another interventional (drug/device) clinical trial.
• Experienced an SAE (serious adverse event) related to scAAV9/JeT-GAN while participating in the first GAN IT study.
• Contraindication to scAAV9/JeT-GAN or any of its ingredients.
• Contraindication to any of the immune suppression medications used in this study.
• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Children's Health

Dallas, Texas, 75235, United States

RECRUITING

Related Publications (4)

• Ding J, Allen E, Wang W, Valle A, Wu C, Nardine T, Cui B, Yi J, Taylor A, Jeon NL, Chu S, So Y, Vogel H, Tolwani R, Mobley W, Yang Y. Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport. Hum Mol Genet. 2006 May 1;15(9):1451-63. doi: 10.1093/hmg/ddl069. Epub 2006 Mar 24.

  PMID: 16565160 BACKGROUND

• Bailey RM, Armao D, Nagabhushan Kalburgi S, Gray SJ. Development of Intrathecal AAV9 Gene Therapy for Giant Axonal Neuropathy. Mol Ther Methods Clin Dev. 2018 Feb 15;9:160-171. doi: 10.1016/j.omtm.2018.02.005. eCollection 2018 Jun 15.

  PMID: 29766026 BACKGROUND

• Weber T. Anti-AAV Antibodies in AAV Gene Therapy: Current Challenges and Possible Solutions. Front Immunol. 2021 Mar 17;12:658399. doi: 10.3389/fimmu.2021.658399. eCollection 2021.

  PMID: 33815421 BACKGROUND

• Bharucha-Goebel DX, Todd JJ, Saade D, Norato G, Jain M, Lehky T, Bailey RM, Chichester JA, Calcedo R, Armao D, Foley AR, Mohassel P, Tesfaye E, Carlin BP, Seremula B, Waite M, Zein WM, Huryn LA, Crawford TO, Sumner CJ, Hoke A, Heiss JD, Charnas L, Hooper JE, Bouldin TW, Kang EM, Rybin D, Gray SJ, Bonnemann CG; GAN Trial Team. Intrathecal Gene Therapy for Giant Axonal Neuropathy. N Engl J Med. 2024 Mar 21;390(12):1092-1104. doi: 10.1056/NEJMoa2307952.

  PMID: 38507752 RESULT

MeSH Terms

Conditions

Giant Axonal Neuropathy; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Peripheral Nervous System Diseases; Neuromuscular Diseases; Polyneuropathies; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Central Study Contacts

Samantha Bridges, BSN

CONTACT

214-456-3696; samantha.bridges@utsouthwestern.edu

Kristy Riddle, BSN

CONTACT

214-456-9501; Kristy.Riddle@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: April 22, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): June 30, 2032
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (1)