Aromatic L-amino Acid Decarboxylase (AADC) DeficiencyEarly Phase 1NCT05765981
An Early Clinical Trial to Evaluate VGN-R09b for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency.
A Early Phase 1 study testing VGN-R09b in people with Aromatic L-amino Acid Decarboxylase (AADC) Deficiency, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
This early Phase trial is to prove the safety and efficacy of VGN-R09b to treat patients with AADC deficiency. Read more about this study
- Who is it for?
- Ages 24 months to 7 years
- Conditions the study is for
- Aromatic L-amino Acid Decarboxylase (AADC) Deficiency
- What is being tested?
- VGN-R09b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 30 Jan 2023to 20 Feb 2029
- Phase
- Early 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 24 months to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- The child patient has to be ≥2 years old and < 8 years old, or a head circumference big enough for surgery.
- Historical diagnosis of AADC deficiency with clinical symptoms consistency, AND confirmed by one of the lab tests: (1) CSF neurotransmitter profile demonstrating reduced HVA and 5-HIAA, and elevated L-Dopa concentrations; (2) Plasma AADC activity less than or equal to 5 pmol/min/mL, AND with Molecular genetic confirmation of homozygous or compound heterozygous mutation of IVS6+4A>T in DDC.
- Motor development at baseline ≤3 months, and Failed to benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor or related form of Vitamin B6) at discretion of investigators.
- Stable medication regimen for treatment of AADC deficiency: (i.e. no new medications introduced for at least 6 months, and no existing medication dose changes for at least 3 months prior to Baseline).
- Parent(s)/legal guardian(s) with custody of subject must give their consent for subject to enroll in the study
- Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.
Who cannot join
- Intracranial neoplasm or any structural brain abnormality or lesion (e.g., severe brain atrophy, white matter degenerative changes), which, in the opinion of the study investigators, would confer excessive risk and/or inadequate potential for benefit.
- Presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk (including congenital heart disease, respiratory disease with home oxygen requirement, history of serious anesthesia complications during previous elective procedures, history of cardiorespiratory arrest), liver or renal failure, malignancy, or HIV positive.
- Severe coagulopathy, or need for ongoing anticoagulant therapy.
- clinically active infection or with severe infection within 12 weeks before screening (e.g. adenovirus or herpes virus, pneumonia, sepsis, central nervous system infection).
- Previous stereotactic neurosurgery, or any gene/cell therapy.
- Received live vaccination within 4 weeks.
- Patients with anti-AAV9 neutralizing antibody titer over 1,200 folds.
- Contraindication to sedation during surgery or imaging studies (PET or MRI).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, No. 1678, Dongfang Road, Pudong New Area, Shanghai, 200127
Jiwen Wang, Doctor, 18916613192, wangjiwen@scmc.com.cn
About this study
Official title: An Open, Dose-escalating Early Clinical Trial to Evaluate the Tolerability, Safety, and Efficacy of VGN-R09b by Intra Striatum Injection in Patients With Aromatic L-amino Acid Decarboxylase (AADC) Deficiency.
This early Phase trial is to prove the safety and efficacy of VGN-R09b to treat patients with AADC deficiency.
Read the detailed description
Aromatic L-amino acid decarboxylase (AADC) is an enzyme responsible for the final step in the synthesis of neurotransmitters dopamine and serotonin. AADC deficiency is a rare genetic disorder. VGN-R09b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human AADC (hAADC) being injected directly into striatum.
This is a single-center, open, dose-climbing investigator-sponsored early-stage clinical study that included a dose-climbing phase and a dose-expanding phase.
This study is to give preliminary evidence for the safety and efficacy of VGN-R09b treatment for patients with Aromatic L-amino acid decarboxylase (AADC) deficiency.
- Being tested
- VGN-R09b
- Keywords
- AADC, AAV9, CNS gene therapy
- Medical subject headings
- Aromatic amino acid decarboxylase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VGN-R09bDrug
VGN-R09b will be injected into bilateral putamen by stereotactic surgery.（Through the SmartFlow Ventricular Cannula or the parenchymal injection tube actually used in the research center）
| Study group | Role | What they receive |
|---|---|---|
| Aromatic L-amino acid decarboxylase (AADC) deficiency | Experimental | This early Phase trial is to prove the safety and efficacy of VGN-R09b to treat patients with AADC deficiency. Receives: Drug: VGN-R09b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Measured: Week 52
Achievement Ratio of the four motor development milestones (Head control, Sit independently, Stand/stepping with support and Walk with minimal assistant)
Achievement Ratio of the four motor development milestones (Head control, Sit independently, Stand/stepping with support and Walk with minimal assistant) according to PDMS-II score.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study start30 Jan 2023
- Primary completion20 Feb 2025 (estimated)
- Study completion20 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aromatic L-amino Acid Decarboxylase (AADC) DeficiencyStudies of the same condition, open and under way.
- More trials run by Shanghai Jiao Tong University School of MedicineThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Vitalgen BioPharma Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Jiwen Wang, Doctor, Study chair, Shanghai Children's Medical Center, affiliated to Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05765981
- Sponsor's protocol ID
- VGN-R09b-001
- Status last verified
- Mar 2023
- First submitted
- 18 Jan 2023
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Han F, Gao P, Zhou Y, Cui T, Xu Y, Fang X, Shen M, Dong S, Zhong Y, Wang Y, Bu L, Chen L, Xia Y, Yao R, Bao N, Xue B, Tao Y, Ge J, Ju Z, Zhu Y, Guan Y, Zuo C, Sun X, Ding S, Cao G, Wang X, Feng L, Mao H, Lv H, Zhao X, Li W, Wang J, Song Y. Intraputaminal AAV9 co-delivery of AADC and GDNF in severe AADC deficiency: first-in-human pediatric dose-escalation study. Sci China Life Sci. 2026 Sep 21. doi: 10.1007/s11427-026-3407-8. Online ahead of print.
PubMed 42773379
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Dose-escalating Early Clinical Trial to Evaluate the Tolerability, Safety, and Efficacy of VGN-R09b by Intra Striatum Injection in Patients With Aromatic L-amino Acid Decarboxylase (AADC) Deficiency.
- ClinicalTrials.gov ID
- NCT05765981
- Acronym / sponsor ID
- VGN-R09b-001
- Keywords
- AADC, AAV9, CNS gene therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Collaborators
- Shanghai Vitalgen BioPharma Co., Ltd.
- Study start
- 30 Jan 2023 (actual)
- Primary completion
- 20 Feb 2025 (estimated)
- Study completion
- 20 Feb 2029 (estimated)
- First posted
- 13 Mar 2023 (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.
This early Phase trial is to prove the safety and efficacy of VGN-R09b to treat patients with AADC deficiency.
Detailed description
Aromatic L-amino acid decarboxylase (AADC) is an enzyme responsible for the final step in the synthesis of neurotransmitters dopamine and serotonin. AADC deficiency is a rare genetic disorder. VGN-R09b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human AADC (hAADC) being injected directly into striatum.
This is a single-center, open, dose-climbing investigator-sponsored early-stage clinical study that included a dose-climbing phase and a dose-expanding phase.
This study is to give preliminary evidence for the safety and efficacy of VGN-R09b treatment for patients with Aromatic L-amino acid decarboxylase (AADC) deficiency.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aromatic L-amino acid decarboxylase (AADC) deficiency | Experimental | Drug: VGN-R09bThis early Phase trial is to prove the safety and efficacy of VGN-R09b to treat patients with AADC deficiency. |
Who may qualify
- Ages
- 24 months to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- The child patient has to be ≥2 years old and < 8 years old, or a head circumference big enough for surgery.
- Historical diagnosis of AADC deficiency with clinical symptoms consistency, AND confirmed by one of the lab tests: (1) CSF neurotransmitter profile demonstrating reduced HVA and 5-HIAA, and elevated L-Dopa concentrations; (2) Plasma AADC activity less than or equal to 5 pmol/min/mL, AND with Molecular genetic confirmation of homozygous or compound heterozygous mutation of IVS6+4A>T in DDC.
- Motor development at baseline ≤3 months, and Failed to benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor or related form of Vitamin B6) at discretion of investigators.
- Stable medication regimen for treatment of AADC deficiency: (i.e. no new medications introduced for at least 6 months, and no existing medication dose changes for at least 3 months prior to Baseline).
- Parent(s)/legal guardian(s) with custody of subject must give their consent for subject to enroll in the study
Key exclusion criteria (8 listed)
- Intracranial neoplasm or any structural brain abnormality or lesion (e.g., severe brain atrophy, white matter degenerative changes), which, in the opinion of the study investigators, would confer excessive risk and/or inadequate potential for benefit.
- Presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk (including congenital heart disease, respiratory disease with home oxygen requirement, history of serious anesthesia complications during previous elective procedures, history of cardiorespiratory arrest), liver or renal failure, malignancy, or HIV positive.
- Severe coagulopathy, or need for ongoing anticoagulant therapy.
- clinically active infection or with severe infection within 12 weeks before screening (e.g. adenovirus or herpes virus, pneumonia, sepsis, central nervous system infection).
- Previous stereotactic neurosurgery, or any gene/cell therapy.
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 |
|---|---|---|
| VGN-R09bVGN-R09b will be injected into bilateral putamen by stereotactic surgery.（Through the SmartFlow Ventricular Cannula or the parenchymal injection tube actually used in the research center） | Drug | Aromatic L-amino acid decarboxylase (AADC) deficiency |
Primary outcome
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Time frame: Week 52
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Achievement Ratio of the four motor development milestones (Head control, Sit independently, Stand/stepping with support and Walk with minimal assistant)
Time frame: Week 52
Achievement Ratio of the four motor development milestones (Head control, Sit independently, Stand/stepping with support and Walk with minimal assistant) according to PDMS-II score.
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 13 Mar 2023.
- Derived from this study: PubMed 42773379Han F, Gao P, Zhou Y, Cui T, Xu Y, Fang X, Shen M, Dong S, Zhong Y, Wang Y, Bu L, Chen L, Xia Y, Yao R, Bao N, Xue B, Tao Y, Ge J, Ju Z, Zhu Y, Guan Y, Zuo C, Sun X, Ding S, Cao G, Wang X, Feng L, Mao H, Lv H, Zhao X, Li W, Wang J, Song Y. Intraputaminal AAV9 co-delivery of AADC and GDNF in severe AADC deficiency: first-in-human pediatric dose-escalation study. Sci China Life Sci. 2026 Sep 21. doi: 10.1007/s11427-026-3407-8. Online ahead of print.
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Aromatic L-amino Acid Decarboxylase Deficiency
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.
Jiwen Wang, Doctor study chair
Shanghai Children's Medical Center, affiliated to Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing VGN-R09b in people with Aromatic L-amino Acid Decarboxylase (AADC) Deficiency, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
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 6 inclusion and 8 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 13 Mar 2023. 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 China. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Jiwen Wang, Doctor (18916613192, wangjiwen@scmc.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events (AEs), Serious Adverse Events (SAEs) (time frame: Week 52). The study lists 2 primary outcomes in all. 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 NCT05765981, which also lists 1 linked publication.
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 13 Mar 2023.