A Trial to Evaluate Safety and Efficacy of a Product Named VGN-R09b in Severe AADC Deficiency

An Open, Dose-escalating and Dose Confirmation Trial to Evaluate the Safety and Efficacy of VGN-R09b by Intra Putamen Injection in Patients With Severe Aromatic L-amino Acid Decarboxylase (AADC) Deficiency

This trial includes dose-escalating part (phase 1) and dose confirming part, to prove the safety and efficacy of VGN-R09b to treat patients with severe AADC deficiency

Study Overview

• Status: Active, not recruiting
• Conditions: Aromatic L-amino Acid Decarboxylase Deficiency
• Intervention / Treatment: Genetic: VGN-R09b injection

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 putamen.

This is an open, dose-escalating and dose confirming study. The sponsor plans to explore two dose levels (6.0×1011vg and 1.28×1012vg) in dose-escalating phase (three subjects each cohort), then plans to have 10 subjects enrolled for dose confirmation phase.

This study is to give evidence for the safety and efficacy of VGN-R09b treatment for patients with severe Aromatic L-amino acid decarboxylase (AADC) deficiency.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200120
      • Shanghai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The child patient has to be ≥18 months old and < 8 years old, and a head circumference big enough for surgery as judged by investigator.
2. Historical diagnosis of AADC deficiency with clinical symptoms consistency, AND with Molecular genetic confirmation of homozygous or compound heterozygous mutation point of IVS6+4A>T in DDC gene.
3. With Plasma AADC activity less than or equal to 12 pmol/min/mL.
4. Motor development at baseline <3 months (head fully uncontrollable at baseline）, and Failed to benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor or related form of Vitamin B6) at discretion of investigators.
5. Parent(s)/legal guardian(s) with custody of subject must give their consent for subject to enroll in the study.
6. 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.

Exclusion Criteria:

1. 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.
2. 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.
3. Severe coagulopathy, or need for ongoing anticoagulant therapy.
4. clinically active infection or with severe infection within 12 weeks before screening (e.g. adenovirus or herpes virus, pneumonia, sepsis, central nervous system infection).
5. Previous stereotactic neurosurgery, or any gene/cell therapy.
6. Received live vaccination within 4 weeks.
7. Contraindication to sedation during surgery or imaging studies (PET or MRI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VGN-R09b injection; Different levels of VGN-R09b will be injected into bilateral putamen by stereotactic surgery	Genetic: VGN-R09b injection; Two levels of VGN-R09b will be injected into bilateral putamen in dose-escalating phase, and one dose level will be injected in dose confirming phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)	Vital signs, physical examination, laboratory test will be monitored after drug injection	up to Week 52
Number of subjects who achieved motor development milestones	Four milestones, including Head control, Sit independently, Stand/stepping with support, Walk with minimal assistant, would be assessed according to definition in Peabody Developmental Motor Scale 2nd edition (PDMS-2). Each milestone would be scored as 0, 1 or 2, and score 2 means achievement of the milestone.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of Clinical symptoms	Number of disease related symptoms	up to 5 Years
Viral shedding	Concentrations of Viral genome in serum/urine would be measured	up to 1 week
Number of Adverse Events (AEs), Serious Adverse Events (SAEs) in Long-term follow-up	Drug-related AEs and SAEs would be monitored as long as 5 years after injection	up to 5 Years
Change in brain AADC activity	Increase in signal in the putamen and nigra on Fluorodopa-PET imaging as brain AADC activity measure	up to 5 Years
Change in Cerebrospinal Fluid (CSF) neurotransmitter metabolite concentrations	Neurotransmitter metabolite concentrations of Homovanillic Acid/Hydroxyindoleacetic Acid (HVA/5-HIAA) would be measured	up to 5 Years
Immunogenicity after injection	Subject number with positive antibodies of AAV9/AADC/Glial Cell Line-Derived Neurotrophic Factor (GDNF) in blood would be reported	up to 26 weeks
Change from baseline in motor function	Motor function would be assessed by Peabody Developmental Motor Scale 2nd edition (PDMS-2). The score ranges from 0 to 482, and higher score means the better in motor function.	up to 5 Years

Collaborators and Investigators

• Sponsor: Shanghai Vitalgen BioPharma Co., Ltd.
• Investigators: Principal Investigator: yi Wang, MD, Children's Hospital of Fudan University; Principal Investigator: jiwen Wang, MD, Shanghai Children's Medical Center; Principal Investigator: yunhai song, MD, Shanghai Children's Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2024
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): September 20, 2030

Study Registration Dates

• First Submitted: May 17, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: AAV9; AADC; Central Nervous System (CNS) gene therapy
• Additional Relevant MeSH Terms: Aromatic amino acid decarboxylase deficiency
• Other Study ID Numbers: VGN-R09b-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No