An Early Clinical Trial to Evaluate VGN-R09b for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency.

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.

Study Overview

• Status: Recruiting
• Conditions: Aromatic L-amino Acid Decarboxylase (AADC) Deficiency
• Intervention / Treatment: Drug: VGN-R09b

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 Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jiwen Wang, Doctor; Phone Number: 18916613192; Email: wangjiwen@scmc.com.cn

Study Locations

• China
  • No. 1678, Dongfang Road, Pudong New Area, Shanghai
    • Shanghai, No. 1678, Dongfang Road, Pudong New Area, Shanghai, China, 200127
      • Recruiting
      • Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Jiwen Wang, Doctor; Phone Number: 18916613192; Email: wangjiwen@scmc.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The child patient has to be ≥2 years old and < 8 years old, or a head circumference big enough for surgery.
2. 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.
3. 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.
4. 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).
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. Patients with anti-AAV9 neutralizing antibody titer over 1,200 folds.
8. 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: 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.	Drug: VGN-R09b; 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）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)	Number of Adverse Events (AEs), Serious Adverse Events (SAEs)	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.	Week 52

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai Vitalgen BioPharma Co., Ltd.
• Investigators: Study Chair: Jiwen Wang, Doctor, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Anticipated): February 20, 2025
• Study Completion (Anticipated): February 20, 2029

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: AADC, AAV9, CNS gene therapy
• Other Study ID Numbers: VGN-R09b-001

Drug and device information, study documents

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