## Protocol Section
### Identification Module
**NCT ID:** NCT06432140

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

**Official Title:** 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

#### Organization Study ID Info
**ID:** VGN-R09b-102
#### Organization
**Class:** INDUSTRY
**Full Name:** Shanghai Vitalgen BioPharma Co., Ltd.
### Status Module
#### Completion Date
**Date:** 2030-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-29

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-17
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Shanghai Vitalgen BioPharma Co., Ltd.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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

**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.

### Conditions Module

**Conditions:**

- Aromatic L-amino Acid Decarboxylase Deficiency

**Keywords:**

- AADC

- AAV9

- Central Nervous System (CNS) gene therapy

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** VGN-R09b will be injected into bilateral putamen by stereotactic surgery

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 16

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Different levels of VGN-R09b will be injected into bilateral putamen by stereotactic surgery

**Intervention Names:**

- Genetic: VGN-R09b injection

**Label:** VGN-R09b injection

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- VGN-R09b injection

**Description:** 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

**Name:** VGN-R09b injection

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** Vital signs, physical examination, laboratory test will be monitored after drug injection

**Measure:** Number of Adverse Events (AEs), Serious Adverse Events (SAEs)

**Time Frame:** up to Week 52

**Description:** 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)

**Measure:** Number of subjects who achieved motor development milestones

**Time Frame:** up to 24 months

#### Secondary Outcomes

**Description:** Increase in signal in the putamen and nigra on Fluorodopa-PET imaging as brain AADC activity measure

**Measure:** Change in brain AADC activity

**Time Frame:** up to 5 Years

**Description:** Neurotransmitter metabolite concentrations of Homovanillic Acid/Hydroxyindoleacetic Acid (HVA/5-HIAA) would be measured

**Measure:** Change in Cerebrospinal Fluid (CSF) neurotransmitter metabolite concentrations

**Time Frame:** up to 5 Years

**Description:** Motor function would be assessed by Peabody Developmental Motor Scale 2nd edition (PDMS-2)

**Measure:** Change from baseline in motor function

**Time Frame:** up to 5 Years

**Description:** Number of disease related symptoms

**Measure:** Change in number of Clinical symptoms

**Time Frame:** up to 5 Years

**Description:** Concentrations of Viral genome in serum/urine would be measured

**Measure:** Viral shedding

**Time Frame:** up to 1 week

**Description:** Subject number with positive antibodies of AAV9/AADC/Glial Cell Line-Derived Neurotrophic Factor (GDNF) in blood would be reported

**Measure:** Immunogenicity after injection

**Time Frame:** up to 26 weeks

**Description:** Drug-related AEs and SAEs would be monitored as long as 5 years after injection

**Measure:** Number of Adverse Events (AEs), Serious Adverse Events (SAEs) in Long-term follow-up

**Time Frame:** up to 5 Years

### Eligibility Module

**Eligibility Criteria:** 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).

**Maximum Age:** 8 Years

**Minimum Age:** 18 Months

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** GCPwxm666@163.com

**Name:** Xiumin Wang, MD

**Phone:** +86-18017395221

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Shanghai Children's Medical Center, affiliated to Shanghai Jiao Tong University School of Medicine

**Name:** Xiumin Wang, MD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: Rare

- Name: Rare Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: T481

- Name: Aromatic L-amino Acid Decarboxylase Deficiency

- Relevance: HIGH

- As Found: Aromatic L-amino Acid Decarboxylase Deficiency

### Intervention Browse Module - Browse Branches

- Abbrev: AnDyAg

- Name: Anti-Dyskinesia Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M7472

- Name: Dopa Decarboxylase

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
