Evaluating VGN-R09b for treating 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 study is testing a new gene therapy called VGN-R09b to see if it can help people with AADC deficiency by improving their symptoms.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 24 Months to 7 Years
• Sex: All
• Sponsor: Shanghai Jiao Tong University School of Medicine (Academic / other)
• Locations: 1 site (Shanghai, No. 1678, Dongfang Road, Pudong New Area, Shanghai)
• Trial ID: NCT05765981 on ClinicalTrials.gov

What this trial studies

This early Phase 1 trial aims to assess the safety and efficacy of VGN-R09b, a gene therapy using adeno-associated virus serotype 9, for patients with Aromatic L-amino Acid Decarboxylase (AADC) deficiency. The study involves a single-center, open-label design with a dose-climbing phase followed by a dose-expanding phase. Participants will receive direct injections of VGN-R09b into the striatum to evaluate its potential benefits in addressing this rare genetic disorder affecting neurotransmitter synthesis.

Who should consider this trial

Good fit: Ideal candidates for this study are children aged 2 to 8 years diagnosed with AADC deficiency who have not benefited from standard medical therapies.

Not a fit: Patients outside the age range or those who have not been diagnosed with AADC deficiency will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients suffering from AADC deficiency by restoring neurotransmitter levels.

How similar studies have performed: While gene therapy approaches for neurological conditions are emerging, this specific application for AADC deficiency is novel and has not been extensively tested in prior studies.

Eligibility criteria

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).

Where this trial is running

Shanghai, No. 1678, Dongfang Road, Pudong New Area, Shanghai

• Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, No. 1678, Dongfang Road, Pudong New Area, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Jiwen Wang, Doctor

Conditions Aromatic L-amino Acid Decarboxylase Deficiency; AADC, AAV9, CNS gene therapy