Giant Axonal Neuropathy (GAN)Phase 1NCT07543991
Intraneural Administration of scAAV9/JeT-GAN Into the Vagus Nerve for Patients With Giant Axonal Neuropathy (GAN)
A Phase 1 study testing scAAV9/JeT-GAN in people with Giant Axonal Neuropathy (GAN), run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 10 to 25 years
- Conditions the study is for
- Giant Axonal Neuropathy (GAN)
- What is being tested?
- scAAV9/JeT-GAN
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2026to 30 Jun 2032
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Health
Dallas, Texas, 75235
About this study
Official title: 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
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.
Read more
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)
- Being tested
- scAAV9/JeT-GAN
- Keywords
- Giant axonal neuropathy (GAN), Gene Therapy, scAAV9/JeT-GAN, Neurodegenerative disorder, Autonomic Nervous System, Hannah's Hope Fund
- Medical subject headings
- Giant Axonal Neuropathy, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
scAAV9/JeT-GANGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: scAAV9/JeT-GAN |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 years post treatment
Secondary outcomes (2)
Stability or Improvement in Autonomic Nervous Symptoms
Efficacy scAAV9/JeT-GAN will be determined by the stability or improvement in autonomic symptoms measured by the following Patient Reported Outcome Measures (PROM):
- The COMPASS-31 is a scale used to measure neurodegenerative system symptoms related to autonomic dysfunction. A higher score indicates worse autonomic dysfunction.
It consists of 31 patient-reported questions across six weighted domains.:
- Orthostatic Intolerance (10 points): Assesses symptoms related to standing up, such as dizziness or fainting.
- Vasomotor Symptoms (6 points): Evaluates issues like changes in skin color or temperature regulation.
- Secretomotor Symptoms (7 points): Focuses on dryness of eyes and mouth.
- Gastrointestinal Symptoms (28 points): Covers digestive issues.
- Bladder Symptoms (9 points): Assesses urinary symptoms.
- Pupillomotor Symptoms (15 points): Relates to pupillary function.
Measured: 3 years post treatment
Stability or Improvement of Motor Function
The Motor Function Measurement-32 (MFM-32) is a clinician-reported outcome measure used to assess the functional abilities of individuals with neuromuscular diseases.
The MFM32 assessment is comprised of 32 items that assess a range of different motor functional abilities across three functional domains:
- Standing and transfers (D1: 13 items),
- Axial and proximal motor function (D2: 12 items)
- Distal motor function (D3: 7 items).
These domains assess a broad spectrum of abilities including gross and distal motor functioning of the upper and lower limbs. Each MFM32 item is scored on a 4-point Likert scale from 0 (cannot initiate the task) to 3 (performs the task fully). Item scores are summed, and the raw score is transformed to an overall total score ranging from 0 (severe functional impairment) to 100 (no functional impairment).
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2026
- Study start1 Mar 2026
- Primary completion31 Dec 2031 (estimated)
- Study completion30 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Giant Axonal Neuropathy (GAN)Studies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Susan T Iannaccone, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07543991
- Sponsor's protocol ID
- STU20250052
- Status last verified
- Apr 2026
- First submitted
- 12 Mar 2026
- Last updated
- 22 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: At this time, the study team is undecided about sharing any patient related data with anyone outside of the study site. Should it be determined that the information learned in this study will be beneficial to other researchers, we make our data available and will follow all regulations regarding data sharing.
Publications
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.
PubMed 16565160Bailey 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.
PubMed 29766026Weber 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.
PubMed 33815421Bharucha-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.
PubMed 38507752
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07543991
- Acronym / sponsor ID
- STU20250052
- Conditions
- Giant Axonal Neuropathy (GAN)
- Keywords
- Giant axonal neuropathy (GAN), Gene Therapy, scAAV9/JeT-GAN, Neurodegenerative disorder, Autonomic Nervous System, Hannah's Hope Fund
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 4 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2026 (actual)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 30 Jun 2032 (estimated)
- First posted
- 22 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label administration of scAAV9/JeT-GAN | Experimental | Genetic: scAAV9/JeT-GANPatients 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. |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of GAN disease by:
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| scAAV9/JeT-GANThe 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. | Genetic | Open Label administration of scAAV9/JeT-GAN |
Primary outcome
Safety of scAAV9/JeT-GAN when delivered to the Vagus Nerve - Based on the Number and Severity of Adverse Events Attributable to Toxicity
Time frame: 3 years post treatment
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
2 secondary outcomes
Stability or Improvement in Autonomic Nervous Symptoms
Time frame: 3 years post treatment
Stability or Improvement of Motor Function
Time frame: 2 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Background: PubMed 16565160Ding 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.
- Background: PubMed 29766026Bailey 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.
- Background: PubMed 33815421Weber 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.
- Results publication: PubMed 38507752Bharucha-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.
- Individual participant dataSharing planned: Undecided. At this time, the study team is undecided about sharing any patient related data with anyone outside of the study site. Should it be determined that the information learned in this study will be beneficial to other researchers, we make our data available and will follow all regulations regarding data sharing.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing scAAV9/JeT-GAN in people with Giant Axonal Neuropathy (GAN), run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Samantha Bridges, BSN (214-456-3696, samantha.bridges@utsouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of scAAV9/JeT-GAN when delivered to the Vagus Nerve - Based on the Number and Severity of Adverse Events Attributable to Toxicity (time frame: 3 years post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07543991, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.